JIMD Podcasts: Recent Episodes

Journal of Inherited Metabolic Disease

A fortnightly podcast from the Journal of Inherited Metabolic Disease, where authors discuss recent publications from the journal. The podcast is intended for specialists and interested clinicians but is also intended to increase the accessibility of this work for patients and families. Supported by Wiley.

Research Round-Up: Sterols and Bile Acids by Journal of Inherited Metabolic Disease

Júlio César Rocha, Anne Daly and Anita MacDonald discuss how nutritional management can move beyond metabolic control towards better lifelong health. From protein substitutes and point-of-care monitoring to new therapies and AI, what might the future look like?From Control to Optimisation: Evolving Strategies in the Nutritional Management of Inborn Errors of Protein MetabolismJúlio César Rocha, Anne Daly, Anita MacDonaldhttps://doi.org/10.1002/jimd.70123

Sarah Firman explores how dietary management can rapidly reduce phytanic acid levels in adult Refsum disease. This case series shows why adequate energy and carbohydrate intake, and avoiding weight loss and catabolism, matter alongside phytanic acid restriction.Adult Refsum Disease: Case Series of Reducing Circulating Phytanic Acid Levels With Dietary InterventionsSarah J. Firman, et alhttps://doi.org/10.1002/jmd2.70048

Are inherited metabolic disorders more common, and less predictable, than we previously thought?Large-scale genomic studies are identifying adults with disease-associated variants who have escaped diagnosis, sometimes despite lifelong symptoms. At the same time, expanding genomic newborn screening risks identifying children who may remain well for decades or never develop clinically significant disease at all.In this episode Dr Nina Gold, Dr Jessica Gold, and Professor Mirjam Langeveld, explore the tension between missed diagnosis and overdiagnosis and ask, when does knowing more genuinely help?Are Inherited Metabolic Disorders More Common and Less Predictable Than We Thought?N Gold et alhttps://doi.org/10.1002/jimd.70094Screening for Life: Perspectives From Adult Metabolic Specialists on Newborn Screening for Inherited Metabolic Diseases.M Langeveld, et al. https://doi.org/10.1002/jimd.70057Exclusion-based exome sequencing in critically ill adults 18–40 years old has a 24% diagnostic rate and finds racial disparities in access to genetic testing.American Journal of Human GeneticsJ Gold et alhttps://www.cell.com/ajhg/fulltext/S0002-9297(25)00238-1Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening.Gold NB, et al.https://www.medrxiv.org/content/10.64898/2026.06.10.26355380v1 - pre-print not peer reviewed

Phenylketonuria (PKU) was one of the first inherited metabolic disorders to be recognised, but there is still plenty to discover. Silvia Radenkovic and Rodrigo Starosta are joined by Dr Cary Harding and Dr Wendy Smith to discuss evolving treatments, updated management guidelines and where PKU research is heading next.The views and opinions expressed in this podcast are those of the speakers and do not necessarily reflect those of their institutions or organisations.

A study of rapamycin in Niemann-Pick C raises an important question: what if the success of a treatment depends on a patient's wider genetic background? Dr Andrés Klein discusses pharmacogenomics, modifier genes and why precision medicine may need to go far beyond making the diagnosis.A Rapamycin Pharmacogenomic Approach for the Childhood Dementia Niemann-Pick CBenjamín Szenfeld, et alhttps://doi.org/10.1002/jimd.70214

In this JIMD Shortcast, first author Arty Selvanathan discusses their study exploring how clinical outcomes relate to biochemical findings in cobalamin C (cblC) disease. What can biochemical markers really tell us about disease severity, and where do their limitations lie?Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C DiseaseArthavan Selvanathan, et alhttps://doi.org/10.1002/jmd2.70091

How much of metabolic control in methylmalonic acidemia is determined by diet, and how much by the microbiome? In this episode, Engin Köse discusses a prospective longitudinal study exploring protein composition, gut microbial changes, and the impact of metronidazole on biochemical control in MMA.Dietary Protein Modulation, Gut Microbiota, and Metabolic Control in Methylmalonic Acidemia: A Prospective Longitudinal StudyEngin Köse, et alhttps://doi.org/10.1002/jimd.70172

In this Shortcast Dr Mark Wijnen presents two cases where Teriparatide was used to treat bone complications in MPD IVB but explains how temporally associated cardiac disease compels his groups to advise caution in its use. Teriparatide in Two Patients With Mucopolysaccharidosis Type IVBMark Wijnen, Evert F. S. van Velsen, J. Gert-Jan Milhous, Esmee Oussoren, Bram C. J. van der Eerden, Margreet A. E. M. WagenmakersFirst published: 13 April 2026 https://doi.org/10.1002/jmd2.70088

A raised glycine level can point to a surprisingly broad range of conditions.In this episode, James Nurse is joined by Arthavan Selvanathan and Curtis Coughlin to discuss their review, The History and Nosology of the Glycine Disorders: A Framework for Clinicians. Together they explore why not all hyperglycinaemia is nonketotic hyperglycinaemia (NKH), how our understanding of glycine disorders has evolved, and how clinicians can navigate the differential diagnosis of elevated glycine in practice.From classic and attenuated NKH to lipoate deficiency syndromes, pyridoxine-related disorders, and important phenocopies such as valproate exposure, this episode provides a practical framework for approaching high glycine levels.The History and Nosology of the Glycine Disorders: A Framework for CliniciansArthavan Selvanathan, et alhttps://doi.org/10.1002/jimd.70138

Season 2 of the JIMD Research Round-Up begins with a deep dive into classical homocystinuria (CBS deficiency). Hosts Silvia Radenkovic and Rodrigo Starosta are joined by two internationally recognised experts, Dr Andrew Morris (Royal Manchester Children's Hospital, UK) and Professor Kim Chapman (Children's Hospital Los Angeles, USA).In this episode, they explore: - The clinical spectrum of homocystinuria, from childhood presentations to adults diagnosed after thrombosis - Why the condition is still frequently missed or misdiagnosed - The overlap with Marfan syndrome and the unanswered questions surrounding disease mechanisms - The strengths and limitations of current newborn screening programmes - Dietary treatment, pyridoxine responsiveness, and the challenges faced by patients and families - Emerging therapies including enzyme substitution therapy, chaperone therapies, and ongoing clinical trials - Why there is genuine optimism for the future of homocystinuria care and researchA fascinating discussion covering six decades of progress in homocystinuria and the next generation of treatments that may transform care.

A new international case series revisits the natural history of D-bifunctional protein deficiency, showing that survival into adolescence and adulthood is possible and that normal VLCFA levels do not exclude the diagnosis. Dr James Nurse speaks with Dr Unai Díaz-Moreno and Dr Spyros Batzios about expanding phenotypes, genotype–phenotype correlations, and the growing role of early genetic diagnosis.From Neonatal Encephalopathy to Adult Survival: Revisiting the Natural History of D-Bifunctional Protein Deficiency in a Multicentre International Case SeriesU. Diaz-Moreno, et alhttps://doi.org/10.1002/jimd.70118

Two adult siblings with unexplained liver disease, renal complications and intermittent haematological abnormalities but with one feature that seemed to argue against a metabolic diagnosis. In this Metabolic Mystery, Dr Greg Lynch explores how an attenuated presentation delayed recognition of the underlying disorder for years.Read the paper: https://doi.org/10.1002/jmd2.70079

Professor Troy Lund and Professor Stephan Kemp discuss the Grey Zone Project and a risk-based framework for interpreting ABCD1 variants in X-linked adrenoleukodystrophy. The episode explores how integrating biochemical, clinical, and longitudinal data may help refine risk stratification and reduce uncertainty in newborn screening.The Grey Zone Project: Risk-Based Classification of ABCD1 Variants in X-Linked AdrenoleukodystrophyTroy C. Lund, et alhttps://doi.org/10.1002/jimd.70157

Too Much of a Good Thing - A 57-year-old man presents with rapidly progressive confusion, but the diagnosis isn’t where most adult physicians would look.Follow the step-by-step clinical reasoning with Dr Mark Wijnen and see if you can solve it.Read the paper: https://www.nejm.org/doi/full/10.1056/NEJMcps2510060

In this episode, Kyle Landskroner and Jagdeep S. Walia talk about their paper on nizubaglustat in a mouse model of GM2 gangliosidosis. They explore how this brain-penetrant dual GCS/NLGase inhibitor improved survival, motor function, and neuroinflammatory markers in Sandhoff disease mice, and what that could mean for future therapies in GM2 disease.Therapeutic Effects of Nizubaglustat in a Mouse Model of GM2 GangliosidosisKyle Landskroner, Kshitiz Singh, Melissa Mitchell, Jagdeep S. Waliahttps://doi.org/10.1002/jimd.70130

Dr Tanyel Zubarioglu discusses the case of a young woman with years of severe abdominal pain, neurological symptoms, anxiety, and repeated hospital visits, initially thought to represent familial Mediterranean fever.In this episode, we explore how a simple urine test during an acute attack changed everything, and why some metabolic diagnoses remain hidden in plain sight.Read the paper here: https://link.springer.com/article/10.1186/s13023-026-04308-3

In this episode, Mariya Sigatullina Bondarenko, Thomas Opladen and Ivana Badnjarevic discuss the first international consensus guideline for tyrosine hydroxylase deficiency. They explore diagnosis, treatment, the move away from rigid subtype labels, and why patient experience matters in shaping better care.PROMs link 👉 https://www.proms-ntd.orgConsensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) DeficiencyMariya Sigatullina Bondarenko, et alhttps://doi.org/10.1002/jimd.70106

Sophie Manoy discusses antenatal and neonatal management in carbonic anhydrase VA deficiency, based on a case series of two affected siblings managed from birth without decompensation.Antenatal and Neonatal Management of Siblings With Carbonic Anhydrase VA DeficiencySophie Manoy, et al https://doi.org/10.1002/jmd2.70076

A rare disorder, a surprisingly basic biological question, and a paper that revisits what GLYCTK actually does. Jörn Oliver Sass joins the podcast to discuss D-glyceric aciduria, mitochondrial localization of D-glycerate kinase, and why getting the fundamentals right still matters.Human D-Glycerate Kinase, Encoded by GLYCTK and Deficient in D-Glyceric Aciduria, Is a Mitochondrial EnzymeAnne Korwitz-Reichelt, et alhttps://doi.org/10.1002/jimd.70119

Dr Rory J. Tinker discusses diagnostic delay in mitochondrial disease, showing that most delays occur before clinical suspicion, despite canonical features being documented years earlier. The study highlights opportunities to shorten the diagnostic odyssey through earlier recognition and informatics approaches.Drivers of Diagnostic Delay in Mitochondrial Disease: Missed Recognition of Canonical FeaturesRory J. Tinker, et alhttps://doi.org/10.1002/jmd2.70068

mRNA therapy is emerging as a serious therapeutic platform for liver inherited metabolic diseases. In this episode, James Nurse speaks with Sonam Gurung and Julien Baruteau about their JIMD paper exploring how mRNA can be used for protein replacement, how lipid nanoparticles help target the liver, and where this approach may complement gene therapy, transplantation and standard care. A clear look at a rapidly evolving field.Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic DiseasesSonam Gurung, et al https://doi.org/10.1002/jimd.70078

Dr Aaron B. Bowen explores epilepsy and EEG features in succinate dehydrogenase (complex II) deficiency, focusing on refractory epilepsy and the presence of RHADS, an EEG pattern more commonly associated with POLG-related disease, and what this means for diagnosis and differential thinking in mitochondrial disorders. Epilepsy Phenotype and EEG Finding of Rhythmic High-Amplitude Delta With Superimposed Spikes (RHADS) in Succinate Dehydrogenase DeficiencyAaron B. Bowen, et alhttps://doi.org/10.1002/jmd2.70072

We talk with Eduardo Vieira Neto about elamipretide in mitochondrial trifunctional protein deficiency and the emerging role of cardiolipin remodelling beyond classic fatty-acid oxidation. Could this offer an add-on approach for complications that triheptanoin doesn’t fully address?Elamipretide Improves Mitochondrial Function in Mitochondrial Trifunctional Protein-Deficient Mice and Human FibroblastsEduardo Vieira Neto, et alhttps://doi.org/10.1002/jimd.70132

Dr Molly Crenshaw shares a powerful neonatal case of treatable molybdenum cofactor deficiency, where rapid biochemical diagnosis preceded molecular confirmation—but the infant deteriorated before disease-altering therapy could be started. This Shortcast highlights the critical value of urgent biochemical testing, evolving therapies, and the narrowing window for intervention in severe neonatal metabolic disease.Treatable Neonatal Molybdenum Cofactor Deficiency: Rapid Demise Despite Rapid Biochemical DiagnosisMolly M. Crenshaw, et alFirst published: 11 January 2026 https://doi.org/10.1002/jmd2.70061

A systems-level exploration of methylmalonic aciduria using personalized genome-scale metabolic models. Featuring Almut Heinken, Vito Zanotelli, and Jean-Louis Guéant, discussing fibroblast transcriptomics, TCA cycle anaplerosis, heme biosynthesis flux, and the promise of multi-omics-guided precision medicine.Personalized Genome-Scale Modeling Reveals Metabolic Perturbations in Fibroblasts of Methylmalonic Aciduria PatientsAlmut Heinken, et alhttps://doi.org/10.1002/jimd.70077

In this Shortcast, Sophie Manoy summarises a newly reported case of holocarboxylase synthetase deficiency presenting with neonatal cholestatic liver disease. This is only the second such case described and highlights a possible genotype–phenotype correlation that broadens the recognised clinical spectrum of this rare but treatable disorder.Holocarboxylase Synthetase Deficiency: A Second Case Report With Neonatal Cholestatic Liver DiseaseSophie Manoy, et alhttps://doi.org/10.1002/jmd2.70051

be a default option? An opinionPeter W Stacpoole, Stephen D Cederbaumhttps://doi.org/10.1016/j.ymgme.2025.109264

In this Shortcast, Dr Herodes Guzman discusses a striking case series of patients with GSDIa who developed fulminant metabolic crisis with persistent lactic acidosis despite correction of hypoglycaemia, raising concern for secondary mitochondrial dysfunction. He explores how these observations challenge conventional management and suggest a future role for mitochondrial-directed surveillance and therapies in GSD care.Retrospective Case Series of Fulminant Metabolic Crisis in GSDIA: Persistent Lactic Acidosis Despite Correction of Hypoglycemia May Reflect Secondary Mitochondrial DysfunctionHerodes Guzman, et alhttps://doi.org/10.1002/jmd2.70059

Only around 18% of inherited metabolic diseases have disease-specific treatments, yet palliative care remains strikingly underused. In this episode, Anja Lee and Trine Tangeraas discuss a pan-European survey exploring access, barriers, and how earlier integration of palliative care can transform support for people living with IMDs. Palliative Care for Children and Adults With Inherited Metabolic Disease in Europe: An Underutilised Service for Supportive Treatment and CareAnja Lee, et alhttps://doi.org/10.1002/jimd.70095

Merve Yoldaş Çelik reviews pediatric cell trafficking disorders, a genetically diverse group that can mimic mitochondrial, lysosomal, and glycosylation disease. Using a 14-patient case series (including two novel variants), she highlights shared multisystem patterns and practical gene-specific clues to support a mechanism-based diagnostic approach.A Multisystem Perspective of Pediatric Cell Trafficking Disorders: Within the Cells, Beneath the SignsMerve Yoldaş Çelik, et alhttps://doi.org/10.1002/jmd2.70053

In this episode of the JIMD Podcast, we explore manganese transporter disorders with Dr Karin Tuschl, Dr Suvasini Sharma and Prof John Spencer, covering clinical red flags, MRI clues, EDTA chelation, and the urgent search for safer, oral treatments for hypermanganesemia with dystonia.Consensus of Expert Opinion for the Diagnosis and Management of Hypermanganesaemia With Dystonia 1 and 2Sherry Fang, et alhttps://doi.org/10.1002/jimd.70031Removal of Toxic Metabolites—Chelation: Manganese DisordersHendrik Vogt, et alhttps://doi.org/10.1002/jimd.70107

Dr Jeremy Clark unpacks why leukodystrophy caused by biallelic HMBS variants does not respond to liver transplantation or hepatically targeted therapies, pointing instead to CNS-driven porphyrin toxicity and a need for entirely new management approaches.Liver Transplantation and Other Hepatically Directed Therapies Do Not Change the Biochemical Phenotype nor Halt Progression of Leukodystrophy due to Biallelic HMBS Variants: A Case ReportJeremy Clark, et alhttps://doi.org/10.1002/jmd2.70056

Join us for a rare conversation with Professors Jean-Marie Saudubray and Manuel Schiff as they reflect on six decades of progress in inherited metabolic diseases, from the earliest chromatograms to the dawn of genomic medicine. This episode explores the discoveries, collaborations, and human stories that shaped the field and continue to guide its future.A Brief History of Inherited Metabolic Diseases: A Personal 60 Years Clinical FlashbackJean-Marie Saudubray, Manuel Schiffhttps://doi.org/10.1002/jimd.70063

In this episode of the JIMD Podcast, Terry G. J. Derks, Alessandro Rossi, Sarah C. Grünert and Yunkoo Kang talk about the evolving role of continuous glucose monitoring (CGM) in liver glycogen storage diseases. The conversation spans international consensus on CGM use and an exciting deep-learning approach to predicting hypoglycaemia, pointing towards more personalised and preventive care for people living with GSD.State of the Art and Consensus Statements by Healthcare Providers, Patients, and Caregivers on Continuous Glucose Monitoring in Liver Glycogen Storage DiseasesTerry G. J. Derks, et alhttps://doi.org/10.1002/jimd.70040 and A deep learning approach for blood glucose monitoring and hypoglycemia prediction in glycogen storage diseaseJi Seung Ryu, et alhttps://www.nature.com/articles/s41598-025-97391-8

A child with severe developmental delay and an early-onset tumour sets the stage for a remarkable case of genetic investigation. In this episode, Sally Ann Lynch and Alfonso D’Alessio uncover how functional testing transformed an uncertain variant into a key diagnostic insight.Read the article: https://doi.org/10.1002/ajmg.a.64275

Krista Casazza talks about validating key biomarkers in Niemann-Pick type C and why they are essential for future clinical trials and regulatory approval. The discussion focuses on emerging candidates such as 24-hydroxycholesterol, neurofilament light chain, and calbindin-D, alongside the urgent need for data harmonisation and collaboration across the NPC community.Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory AlignmentKrista Casazza, et alhttps://doi.org/10.1002/jimd.70075

In this JIMD Shortcast, Allyson Terrell and Katie Sapp explore the real-world challenges of newborn screening for lysosomal storage disorders, based on a survey of healthcare professionals working at the front line of implementation. The study highlights the limitations of single-tier screening, the value of multi-tier testing, and the growing importance of multidisciplinary collaboration to improve diagnostic clarity and patient outcomes.Exploratory Study on the Challenges of Newborn Screening for Lysosomal Storage Disorders Emphasizes the Need for Multitier Testing and Collaborative Approaches to ManagementA. Terrell, et alhttps://doi.org/10.1002/jmd2.70027

A nationwide CTX study, a critical treatment window, and a conversation with the lead author. Dr Tanyel Zübarioğlu joins the JIMD Podcast to unpack the long-term impact of CDCA therapy and why timing matters more than ever.Long-Term Outcomes of Chenodeoxycholic Acid Therapy for Cerebrotendinous Xanthomatosis: A Nationwide Study on Prognostic Factors and Treatment Tanyel Zubarioglu, et alhttps://doi.org/10.1002/jimd.70069Editorial Comment to Regulatory NewsCarla E. M. Hollak, Natalja Bouwhuishttps://doi.org/10.1002/jimd.70071

The Research Round-Up returns! Hosts Silvia Radenkovic and Rodrigo Starosta are joined by Dr Hilary Vernon and Dr Austin Larson for a deep dive into the latest discoveries in mitochondrial disease.Together they explore how new biomarkers like FGF21 and GDF15 are reshaping diagnosis, how multi-omics approaches are accelerating precision care, and what large-scale data from gnomAD to stem-cell models is revealing about disease mechanisms and therapeutic opportunities.A lively, expert-led discussion connecting science, diagnostics, and patient impact across the mitochondrial field.Laricchia KM, et alMitochondrial DNA variation across 56,434 individuals in gnomAD. Genome Res. 2022 Mar;32(3):569-582. doi: 10.1101/gr.276013.121. Epub 2022 Jan 24. PMID: 35074858; PMCID: PMC8896463. Liu O, et alFGF21 and GDF15 are elevated in Barth Syndrome and are correlated to important clinical measures. Mol Genet Metab. 2023 Nov;140(3):107676. doi: 10.1016/j.ymgme.2023.107676. Epub 2023 Aug 2. PMID: 37549445. Van Hove JLK, et alProtein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases. Hepatol Commun. 2024 Jan 5;8(1):e0361. doi: 10.1097/HC9.0000000000000361. Erratum in: Hepatol Commun. 2024 Jan 29;8(2):e0390. doi: 10.1097/HC9.0000000000000390. PMID: 38180987; PMCID: PMC10781130. Starosta RT, et alAn integrated multi-omics approach allowed ultra-rapid diagnosis of a deep intronic pathogenic variant in PDHX and precision treatment in a neonate critically ill with lactic acidosis. Mitochondrion. 2024 Nov;79:101973. doi: 10.1016/j.mito.2024.101973. Epub 2024 Oct 15. PMID: 39413893; PMCID: PMC11578067. Jain IH, et alHypoxia as a therapy for mitochondrial disease. Science. 2016 Apr 1;352(6281):54-61. doi: 10.1126/science.aad9642. Epub 2016 Feb 25. PMID: 26917594; PMCID: PMC4860742 Sandlers Y, et alMetabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function. PLoS One. 2016 Mar 25;11(3):e0151802. doi: 10.1371/journal.pone.0151802. PMID: 27015085; PMCID: PMC4807847. Sniezek Carney O, et al. Stem cell models of TAFAZZIN deficiency reveal novel tissue-specific pathologies in Barth syndrome. Hum Mol Genet. 2025 Jan 23;34(1):101-115. doi: 10.1093/hmg/ddae152. PMID: 39535077; PMCID: PMC11756277.

Baruteau, 2025), reflecting on what this moment tells us about the future of metabolic medicine and how ready we are for it.First in Human Gene Editing for an Inherited Metabolic DiseaseShamima Rahman, Julien Baruteauhttps://doi.org/10.1002/jimd.70056Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic DiseaseKiran Musunuru, et alhttps://www.nejm.org/doi/10.1056/NEJMoa2504747

Dr Samuel Mackenzie discusses the perplexing presentation of a 61-year-old man with rhabdomyolysis and a prolonged QT interval. Further exploration reveals a lifetime of episodic fatigue with illnesses.https://doi.org/10.1016/j.ymgmr.2025.101241

Inherited metabolic diseases aren’t just for the young.James Nurse talks with François Maillot and Ida Schwartz about their systematic review revealing how IMDs can first be diagnosed well into older age. From Fabry disease to alkaptonuria, they discuss diagnostic delays, missed clues, and why it’s time to think about geriatric metabolic medicine.Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature ReviewMaria-Rita Moio, et alhttps://doi.org/10.1002/jimd.70038

With Rodrigo off caring for sick children, James Nurse joins Silvia Radenkovic to speak with Dr Judith Jans and Dr Devin Oglesbee about the emerging field of untargeted metabolomics. Authors’ opinions are their own and do not represent their institutions.Referenced papers include:Miller MJ, et al The emerging role of metabolomics analysis in genetic and genomic testing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jul 17:101493. doi: 10.1016/j.gim.2025.101493. Epub ahead of print.Evans AM, et alDissemination and analysis of the quality assurance (QA) and quality control (QC) practices of LC-MS based untargeted metabolomics practitioners. Metabolomics. 2020 Oct 12;16(10):113. doi: 10.1007/s11306-020-01728-5. Wurth R, et al.An evaluation of untargeted metabolomics methods to characterize inborn errors of metabolism. Mol Genet Metab. 2024 Jan;141(1):108115. doi: 10.1016/j.ymgme.2023.108115. Epub 2023 Dec 15. Haijes HA, et al. Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma. Metabolites. 2019 Jan 11;9(1):12. doi: 10.3390/metabo9010012. Willems AP, et al A one-year pilot study comparing direct-infusion high resolution mass spectrometry based untargeted metabolomics to targeted diagnostic screening for inherited metabolic diseases. Front Mol Biosci. 2023 Nov 2;10:1283083. doi: 10.3389/fmolb.2023.1283083. Haijes HA, et al. Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation. Mol Genet Metab. 2019 Aug;127(4):368-372. doi: 10.1016/j.ymgme.2019.07.001. Epub 2019 Jul 9. PMID: 31311714.Hoegen B, et alApplication of metabolite set enrichment analysis on untargeted metabolomics data prioritises relevant pathways and detects novel biomarkers for inherited metabolic disorders. J Inherit Metab Dis. 2022 Jul;45(4):682-695. doi: 10.1002/jimd.12522. Epub 2022 May 22. PMID: 35546254; PMCID: PMC9544878.Gao Q, et alA diagnostic algorithm for inherited metabolic disorders using untargeted metabolomics. Metabolomics. 2025 Jul 27;21(4):101. doi: 10.1007/s11306-025-02302-7. PMID: 40715884; PMCID: PMC12301266.Kerkhofs MHPM, et al. Cross-Omics: Integrating Genomics with Metabolomics in Clinical Diagnostics. Metabolites. 2020 May 18;10(5):206. doi: 10.3390/metabo10050206. Ashenden AJ, et al. The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges. Int J Neonatal Screen. 2024 Jun 21;10(3):42. doi: 10.3390/ijns10030042.Liu N, et al. Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism. JAMA Netw Open. 2021 Jul 1;4(7):e2114155. doi: 10.1001/jamanetworkopen.2021.14155.

Can small molecules stabilise OTC enzyme activity and change the outlook for urea cycle disorders? Dr Alexander Laemmle (University Hospital Bern) discusses pharmacological chaperones, a novel approach that strengthens enzyme stability in patient-derived liver models and offers new hope for female OTC carriers.Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease ModelsAdhuresa Ramosaj, et alhttps://doi.org/10.1002/jimd.70043Induced pluripotent stem cell technology as diagnostic tool in patients with suspected ornithine transcarbamylase deficiency lacking genetic confirmationAdhuresa Ramosaj et alhttps://doi.org/10.1016/j.ymgmr.2023.101007

Shortcast: Clinical and Developmental Outcomes after 50 Years of Galactosaemia NBS in Ireland by Journal of Inherited Metabolic Disease

In this episode we discuss new insights into the variability of long-term outcomes in classic galactosemia. Joining me are Nikki Smith, Olivia Garrett, and Judy Fridovich-Keil, who together explore how complications in cognitive, motor, and speech domains emerge, cluster, and vary in severity across patients. Their study highlights both patterns and unanswered questions, illustrating the challenges families face and the importance of refining prognostic tools.Patterns of Penetrance and Expressivity of Long-Term Outcomes in Classic GalactosemiaNicole H. Smith et al.https://doi.org/10.1002/jimd.70020

Silvia and Rodrigo are joined by Dr Ray Wang, Director of the multidisciplinary Foundation of Caring Lysosomal Storage Disorder Program at the Children's Hospital of Orange County. Silvia asks Dr Wang and Rodrigo (who also happens to be a researcher in this field) about cutting-edge advances in LSD research: from base editing in Pompe disease and patient-specific in vivo gene editing, to new biomarkers and scoring systems in Gaucher disease, insights into lipid dysregulation across lysosomal storage disorders, and the first clinical trial of anakinra in Sanfilippo syndrome.Papers discussed include:Christensen CL, et alBase editing rescues acid α-glucosidase function in infantile-onset Pompe disease patient-derived cells. Mol Ther Nucleic Acids. 2024 May 21;35(2):102220. doi: 10.1016/j.omtn.2024.102220. PMID: 38948331; PMCID: PMC11214518.Starosta RT, et alPredicting liver fibrosis in Gaucher disease: Investigation of contributors and development of a clinically applicable Gaucher liver fibrosis score. Mol Genet Metab. 2025 Feb;144(2):109010. doi: 10.1016/j.ymgme.2025.109010. Epub 2025 Jan 3. PMID: 39788861.Kell P, et alSecondary accumulation of lyso-platelet activating factors in lysosomal storage diseases. Mol Genet Metab. 2025 Jun 17;145(4):109180. doi: 10.1016/j.ymgme.2025.109180. Polgreen LE, et alAnakinra in Sanfilippo syndrome: a phase 1/2 trial. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21. Erratum in: Nat Med. 2024 Sep;30(9):2693. doi: 10.1038/s41591-024-03207-z. Musunuru K, et al Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med. 2025 Jun 12;392(22):2235-2243. doi: 10.1056/NEJMoa2504747.

What if one enzyme could link metabolism, epigenetics, and therapy across conditions as diverse as epilepsy, cancer, and inflammation?In this episode, we dive into the fascinating world of adenosine kinase (ADK), an ancient enzyme that controls adenosine levels, energy balance, and even DNA methylation. Dr Detlev Boison join us to discuss their recent review in the Journal of Inherited Metabolic Disease, which reframes ADK not just as a metabolic regulator, but as a potential epigenetic drug target.From seizure suppression to cancer immunology, ADK sits at a crossroads, and could be a future key to metabolic and epigenetic medicine.Adenosine Kinase: An Epigenetic Modulator and Drug TargetUchenna Peter-Okaka, Detlev Boisonhttps://doi.org/10.1002/jimd.70033

The first updated Footprints article requires two guests to do it justice - Dr Dakota Peacock and Dr Darius Ebrahimi-Fakhari join Eva Morava to discuss movement disorders in Inherited Metabolic Disease.Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2025.109084Find IMDs associated with psychiatric presentations at: https://www.iembase.org/gamuts/store/docs/Movement_disorders_update.pdf

A newborn with no symptoms, an unexpected X-ray finding, and a puzzle that points in many possible directions. Follow Dr. Tolulope Tolufase as he unpacks a neonatal case where incidental adrenal calcifications conceal a far deeper mystery.Read the full report here: https://doi.org/10.1136/bcr-2025-265278

In this episode, we speak with Irena Muffels and Eva Morava about their recent review, The Therapeutic Future for Congenital Disorders of Glycosylation. We explore the three pillars they propose for advancing CDG treatment: improving disease models, enhancing clinical trial readiness, and finding scalable strategies that move us beyond one-gene-at-a-time approaches. From patient-derived brain organoids to AI-powered outcome assessments and the promise of basket trials, this conversation is a sweeping tour through the innovations shaping the future of CDG care.The Therapeutic Future for Congenital Disorders of GlycosylationI. J. J. Muffels, T. Kozicz, E. O. Perlstein, E. Moravahttps://doi.org/10.1002/jimd.70011

Held (2025)Long-term outcomes of adolescents and young adults identified by metabolic newborn screening. Mütze et al (2025)Treatment Outcomes for Maple Syrup Urine Disease Detected by Newborn Screening. Mengler et al (2024)Vitamin B12 Deficiency Newborn Screening. Mütze et al (2024)The role of exome sequencing in newborn screening for inborn errors of metabolism. Adhikari et al (2020)

In this episode, Sabine Fuchs and Eva Hoytema discuss their recent work exploring the expanding clinical spectrum of aminoacyl-tRNA synthetase deficiencies, highlighting diagnostic challenges and emerging insights into this complex group of rare disorders.Setting the Stage for Treatment of Aminoacyl-tRNA Synthetase (ARS)1-Deficiencies: Phenotypic Characterization and a Review of Treatment EffectsEva M. M. Hoytema van Konijnenburg, et alhttps://doi.org/10.1002/jimd.70017

Marya Sabir shares new insights into the utility of leukocyte sialic acid levels as a diagnostic and monitoring tool in free sialic acid storage disorder.Investigating the Utility of Leukocyte Sialic Acid Measurements in Lysosomal Free Sialic Acid Storage DisorderMarya S. Sabir, et alhttps://doi.org/10.1002/jmd2.70029

Dr Laura Adang returns to the podcast, this time discussing diagnostic delays in early onset forms of metachromatic leukodystrophy and explains why the only logical route to prompt diagnosis is newborn screening and how gene therapy might lead to a 'normal' life for children, if only we can find them early enough.Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data ApproachAli Mohajer, et alhttps://doi.org/10.1002/jimd.70049

Molecular Biology in the College of Medicine at University of Florida, join Rodrigo and Silvia to discuss new insights, AI, cancer metabolism and some of their favourite papers on Glycogen Storage Disorders. Authors opinions are their own and do not represent their institutions.GSD episode papers:Brain glycogen serves as a critical glucosamine cache required for protein glycosylation. Sun et alA machine learning model accurately identifies glycogen storage disease Ia patients based on plasma acylcarnitine profiles. Groen et alSmall-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders. Ullman et alRepurposing SGLT2 inhibitors: Treatment of renal proximal tubulopathy in Fanconi-Bickel syndrome with empagliflozin. Overduin et alGross-ValleThe relation between dietary polysaccharide intake and urinary excretion of tetraglucoside. Gross-Valle et alGlycogen drives tumour initiation and progression in lung adenocarcinoma. Clarke HA et alSpatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis. Conroy et alIn situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues. Young et alGlycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis. Brewer et alDynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants. Rahman MS et alNeurological glycogen storage diseases and emerging therapeuticsColpaert et al

In this latest episode, we explore what's next for treating classic galactosemia. The discussion is anchored in two fascinating recent publications, including the wide-angle perspective from “Reshaping the Treatment Landscape of a Galactose Metabolism Disorder” and a deep dive into something delightfully unexpected: purple sweet potato color (PSPC) as a therapeutic strategy. Yes, purple sweet potatoes. Who knew?We’re joined by familiar voices Estela Rubio-Gozalbo and Kent Lai, alongside first-time guests Synneva HagenLillevik and Bijina Balakrishnan, for a conversation that blends bold scientific possibility with practical insights on the challenges of developing disease-modifying therapies for galactosemia.Reshaping the Treatment Landscape of a Galactose Metabolism DisorderM. Estela Rubio-Gozalbo, et alhttps://doi.org/10.1002/jimd.70013Assessment of Long-Term Safety and Efficacy of Purple Sweet Potato Color (PSPC) and Myo-Inositol (MI) Treatment for Motor Related and Behavioral Phenotypes in a Mouse Model of Classic GalactosemiaOlivia Bellagamba, et alhttps://doi.org/10.1002/jimd.70002

Dr JP Stevens shares the mystery of a 5-year-old boy presenting with severe gastrointestinal bleeding and cholestasis. Inpatient investigation reveals gallbladder polyps and, on assessment after recovery he is found to have signs of developmental delay. Can you recognise the clues in the presentation?https://onlinelibrary.wiley.com/doi/10.1097/PG9.0000000000000122

Lottie Morison joins the podcast to discuss recent insights around speech and language progression and assessment in CLN2 and CLN3 disease. Lottie is the first speech and language pathologist to lead an episode and brilliant exemplifies the multidisciplinary nature of IMD care. Speech, Language and Non-verbal Communication in CLN2 and CLN3 Batten DiseaseLottie D. Morison, et alhttps://doi.org/10.1002/jimd.12838

A special episode of the podcast as we visit the presentation day for the Metbionet Metabolic Minds leadership programme to hear about a plan to safeguard the future of specialist biochemistry services in the UK. Dr Rachel Carling explains the programme and then we hear from three of the course candidates, Dr Alana Burns, Annabel Wong and Freya Hassall about their projects on LSD testing, troubleshooting MS/MS and handling measurement uncertainty.

Dr Luciana Hannibal, Research Group Leader / Head of Translational Metabolomics at the Centre for Integrative Biological Signalling Studies in Freiburg, and Dr Julien Park, a Physician-scientist at the Children's University Hospital Münster, are Rodrigo and Silvia's latest guests, providing a thorough overview of disorders of Redox Metabolism. Authors opinions are their own and do not represent their institutions.Papers discussed include:Targeted Metabolic Profiling of Methionine Cycle Metabolites and Redox Thiol Pools in Mammalian Plasma, Cells and UrineBehringer et alTreatment with 2-phospho-L-ascorbic acid mitigates biochemical phenotypes of heme oxygenase 1 deficiencyBerendes et alGuidelines for measuring reactive oxygen species and oxidative damage in cells and in vivoMurphy et alThe motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1Park et alClinical and molecular analysis of a novel variant in heme oxygenase-1 deficiency: Unraveling its role in inflammation, heme metabolism, and pulmonary phenotypeBerendes et alRedox signaling in inherited diseases of metabolism,Current Opinion in PhysiologyJacobsen and HannbalReal-time detection of enzymatically formed hydrogen sulfide by pathogenic variants of cystathionine beta-synthase using hemoglobin I of Lucina pectinata as a biosensor.Myszkowska et al

Dr Travis Johnson and Dr Sarah Mele join the podcast to explain why flies make great models for Short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) and how their work is shedding light on different treatment modalities.Valine Restriction Extends Survival in a Drosophila Model of Short-Chain Enoyl-CoA Hydratase 1 (ECHS1) DeficiencySarah Mele, et alhttps://doi.org/10.1002/jimd.12840

Dr Mrinmayee Takle and Dr Kuntal Sen discuss the challenging dilemma of a child, presenting from infancy with recurrent seizures and three different (wrong) diagnoses including opsoclonus-myoclonus-ataxia syndrome.Read the article: https://doi.org/10.1002/cns3.20098Mrinmayee Takle, Dhwani Sahjwani, Diana Bharucha-Goebel, Tyler Rapp, Cecilia Bouska, Alexandra Kornbluh, Kuntal Sen

Treatment is available for most intoxication-type disorders, but would you know what to do in an emergency. In this podcast, Dr Dexter Tarr discusses the acute management when these conditions cause encephalopathy, seizures, stroke-like episodes, thromboses, liver failure, cardiac failure, arrhythmias and rhabdomyolysis. Emergency Management of Intoxication-Type Inherited Metabolic DisordersJ. Dexter Tarr, Andrew A. M. Morrishttps://doi.org/10.1002/jimd.70007

Michel Tchan and Mirjam Langeveld join the podcast to look at changes to adult IMD services over the last decade and consider the challenge to develop services to meet the needs of growing patient numbers over the next 10 years.The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: 10 Years Later, Another Report From the SSIEM Adult Metabolic Physicians GroupMichel Tchan, et alhttps://doi.org/10.1002/jimd.70005

Dr Sabine Fuchs, Professor of Metabolic diseases and innovative therapies at the UMC Utrecht, and Dr Sean Froese, a Principal Investigator in the Metabolism Division at University Children’s Hospital Zürich, join Rodrigo and Silvia to discuss new insights and some of their favourite papers on Methylmalonic Aciduria. Authors opinions are their own and do not represent their institutions.Papers discussed include:Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiencyForny et alAberrant methylmalonylation underlies methylmalonic acidemia and is attenuated by an engineered sirtuin.Head et alLipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.Manoli et alPrime editing for functional repair in patient-derived disease modelsSchene et alMutation-specific reporter for optimization and enrichment of prime editingSchene et alBiomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Manoli et alFibroblast growth factor 21 as a biomarker for long-term complications in organic acidemias.Molema et al

Lucas Agnoletto and Dr Rebecca Halligan report work looking at sleep quality in children with hepatic GSDs, considering whether sleep is impacted by poor glycemic control or our efforts to improve this through overnight feeding.Sleep quality in children with hepatic glycogen storage diseases, a prospective observational pilot studyLucas Agnoletto, et alhttps://doi.org/10.1002/jmd2.12462

Dr Carole Linster and Dr Nicole van Bergen explain why metabolism isn't perfect and how disorders of enzyme repair present their own challenges. In an episode that explores Niacin and longevity, we also hear why NAXD deficiency is an important differential in acute cardiomyopathy and provides an aetiology that could be highly amenable to treatment. Clinical and biochemical distinctions for a metabolite repair disorder caused by NAXD or NAXE deficiencyNicole J. Van Bergen, et alhttps://doi.org/10.1002/jimd.12541NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses Nicole J Van Bergen, et alhttps://doi.org/10.1093/brain/awy310Severe NAD(P)HX Dehydratase (NAXD) Neurometabolic Syndrome May Present in Adulthood after Mild Head TraumaNicole J Van Bergen, et alhttps://doi.org/10.3390/ijms24043582

Asthik Biswas, Spyros Batzios, and Kshitij Mankad expand on their recent letter to the editor to explain why ushering in the new era of gene therapy treatments requires not just clinical but also imaging readiness. Imaging readiness in the gene therapy era-exploring standardized protocols for response assessmentAsthik Biswas, et alhttps://doi.org/10.1002/jimd.12828

Dr Matthew Wilson, Postdoctoral Fellow at the Centre for Human Genetics, KU Leuven, joins hosts Silvia Radenkovic and Rodrigo Starosta to discuss a scintillating selection of CDG papers in our first ever research round-up. Authors opinions are their own and do not represent their institutions.The papers discussed include:A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Wilson et alClinical and biochemical footprints of congenital disorders of glycosylation: Proposed nosology. Ng et alRft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane. Chen et alMolecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG. Hirata et alGenome and RNA sequencing were essential to reveal cryptic intronic variants associated to defective ATP6AP1 mRNA processing. Morales-Romero et alN-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts. Garapati et alIn vitro treatment with liposome-encapsulated Mannose-1-phosphate restores N-glycosylation in PMM2-CDG patient-derived fibroblasts. Shirakura et al Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation. Budhraja et alD-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG). Starosta et alGlycoproteomics in Cerebrospinal Fluid Reveals Brain-Specific Glycosylation Changes. Baerenfaenger et alNeural and metabolic dysregulation in PMM2-deficient human in vitro neural models.Radenkovic et alFrontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohortLam et al

It's an Arg1 extravaganza as Reena Sharma, Sara Olofsson, Karolina Stepien and Alison Woodall discuss three separate papers looking at the Salford Royal experience of a cohort of adults with Arginase 1 deficiency and the wider health and societal cost of the condition. Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centreReena Sharma et alhttps://doi.org/10.1002/jmd2.12450Disease burden among patients with Arginase 1 deficiency and their caregivers: A multinational, cross-sectional surveySara Olofsson et alhttps://doi.org/10.1002/jmd2.12456Societal costs and quality of life associated with arginase 1 deficiency in a European setting – a multinational, cross-sectional surveySara Olofsson et alhttps://doi.org/10.1080/13696998.2024.2400856

In this Shortcast, Dr Aya Amer presents the New Zealand experience of using ketone (D,L-3-HB) supplementation in 12 patients (aged 10-50 years) with GLUT1DS.D,L-3-hydroxybutyrate in the treatment of glucose transporter 1 deficiency syndrome (Glut1DS)Aya Amer, et alhttps://doi.org/10.1002/jmd2.12461

Marshall Summar explains why common polymorphisms and basic physiology mean that L-citrulline may have a role in sickle cell disease, bronchopulmonary dysplasia and even asthma.Potential therapeutic uses of L-citrulline beyond genetic urea cycle disordersMarshall Summarhttps://doi.org/10.1002/jimd.12810

Dr Ashlee Stiles discusses the work-up of a 13-month-old girl with hypoglycaemia and discusses the need to balance prompt metabolic work-up with managing the acutely unwell patient in front of you. Critical sample collection is key and don't forget the urine. Read the report here: https://www.sciencedirect.com/science/article/pii/S2214426924000156?via%3Dihub

In this Metabolic Mystery, Dr Eamon McCarron unravels an unexpected diagnosis in a 55-year-man with a 2-year history of dragging his legs, poor balance, and paresthesia along the outer aspect of his right thigh. He underwent various assessments and investigations over the next 3 years before a diagnosis was made. https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.64031#

Dr Jessica Gold discusses observations around executive function in early treated MSUD patients and how this impacts on outcomes around transition to adulthood. Executive and adaptive function impacts long-term outcomes for adults with maple syrup urine diseaseJessica I. Gold, et alhttps://doi.org/10.1002/jimd.12827

Dr Thomas Cassini explains how the Undiagnosed Diseases Network group used advanced sequencing techniques to clarify the genotype in a child with an unusual phenotype for mitochondrial trifunctional protein deficiency.Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicingThomas Cassini, et alhttps://doi.org/10.1002/jmd2.12459

Dr Andrew Morris joins the podcast to discuss insights from 311 patients with CBS deficiency (classical homocystinuria), their response to treatment and clinical outcomes. Cystathionine β-Synthase Deficiency in the E-HOD Registry—Part II: Dietary and Pharmacological TreatmentAndrew A. M. Morris, Jitka Sokolová, Markéta Pavlíková, Florian Gleich, Stefan Kölker, Carlo Dionisi-Vici, Matthias R. Baumgartner, Luciana Hannibal, Henk J. Blom, Martina Huemer, Viktor Kožich, E-HOD Consortiumhttps://doi.org/10.1002/jimd.12844

Eva Hoytema van Konijnenburg and Clara van Karnebeek tell the podcast about the treatabolome an epic project to include all current IMD treatments and add them to the IEMbase. The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!Bibiche den Hollander, et alhttps://doi.org/10.1002/jimd.12835

Nathalie Guffon joins the podcast to discuss alpha-mannosidosis and the long term efficacy of enzyme replacement therapy with velmanse alfa.Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosisNathalie Guffon, et alhttps://doi.org/10.1002/jimd.12799

It seems everyone is talking about autophagy but what is it and what happens when it goes wrong? Hormos Salimi Dafsari, Carlo Dionisi-Vici, and Heinz Jungbluth join the podcast to answer these questions, discuss their experience across 3 (or 2.5) generations of clinical practice and why you never see an obese 100-year-old.An update on autophagy disordersHormos Salimi Dafsari, et alhttps://doi.org/10.1002/jimd.12798

Marie-Thérèse Henke, Alessandro Prigione, and Markus Schuelke get 2025 off to an informative start discussing why so many models exist for Leigh Syndrome, why we need them and how insights from disease models have led to Sildenafil being used in some patients. Disease models of Leigh syndrome: From yeast to organoidsMarie-Thérèse Henke, Alessandro Prigione, Markus Schuelkehttps://doi.org/10.1002/jimd.12804

Dr François Feillet returns to the podcast to discuss the final results of the KAMPER study, evaluating the long-term safety of sapropterin in phenylketonuria (phenylalanine hydroxylase deficiency).Long-term safety of sapropterin in paediatric and adult individuals with phenylalanine hydroxylase deficiency: Final results of the Kuvan® Adult Maternal Paediatric European Registry multinational observational studyFrançois Feillet, et alhttps://doi.org/10.1002/jimd.12796

Dr Sema Kalkan Uçar joins the podcast to discuss the merits of a high protein, high fat diet for the management of patients with Glycogen Storage Disease type 3a.Long-term personalized high-protein, high-fat diet in pediatric patients with glycogen storage disease type IIIa: Evaluation of myopathy, metabolic control, physical activity, growth, and dietary complianceSema Kalkan Uçar, et alhttps://doi.org/10.1002/jimd.12741

Dr Gabriella Horvath returns for her second visit to the podcast, joining Eva Morava to discuss psychiatric presentations of Inherited Metabolic Disease.Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2020.02.007Find IMDs associated with psychiatric presentations at: http://iembase.org/gamuts/store/docs/Psychiatric_IMD_gamuts.pdf

In this Shortcast Antonio Ochoa-Ferraro and Dr Charlotte Dawson share their experience using the medication Volanesorsen with two pregnant women diagnosed with familial chylomicronemia syndrome.Two successful pregnancies in patients taking Volanesorsen for familial chylomicronemia syndromeSubadra Wanninayake, et alhttps://doi.org/10.1002/jmd2.12435

In the latest podcast, Dr Lourdes Desviat provides an overview of the different RNA based therapeutic approaches including how they work and which are showing promise for the management of Urea Cycle Disorders. Exploring RNA therapeutics for urea cycle disordersEva Richard, Ainhoa Martínez-Pizarro, Lourdes R. Desviathttps://doi.org/10.1002/jimd.12807

Dr Hannerieke van den Hout of Erasmus MC joins the podcast to discuss observations from two decades of early treated infantile onset Pompe disease and the evolving nature of the neurological phenotype.Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive functioningvan den Dorpel, et alhttps://doi.org/10.1002/jimd.12736

Callie Ferguson discusses her group's care for a young woman with FBPase deficiency during pregnancy and beyond. Metabolic management of a successful pregnancy and postpartum complications in fructose-1,6-bisphosphatase deficiencyCallie Ferguson, Anita Madison, Ada Hamosh, Celide Koernerhttps://doi.org/10.1002/jmd2.12453

Professor Shamima Rahman and Dr Nandaki Keshavan take us on a whistle stop tour of the different approaches taken to gene therapy in mitochondrial disease and why some may work better than others. Gene therapy for mitochondrial disordersNandaki Keshavan, Michal Minczuk, Carlo Viscomi, Shamima Rahmanhttps://doi.org/10.1002/jimd.12699

Olivia Garrett, Jared Druss, Estela Rubio-Gozalbo, Gerard Berry, and Judith Fridovich-Keil discuss outcomes in classic galactosemia drawn from patient surveys of 92 adults.Health and well-being of maturing adults with classic galactosemiaOlivia S. Garrett, Jared J. Druss, E. Naomi Vos, Yu-Ting Debbie Fu, Stephanie Lucia, Patricia E. Greenstein, Anna Bauer, Jolanta Sykut-Cegielska, Karolina M. Stepien, Cameron Arbuckle, Olga Grafakou, Uta Meyer, Nele Vanhoutvin, Adriana Pané, Annet M. Bosch, Estela Rubio-Gozalbo, Gerard T. Berry, Judith L. Fridovich-Keil https://doi.org/10.1002/jimd.12786

Professor Carlos Ferreira joins Eva Morava to discuss the metabolic cardiovascular disease and explain why cardiac involvement is common in IMDs and when an underlying metabolic should be suspected in a cardiac presentation.Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2020.12.290Find IMDs associated with epilepsies at: http://www.iembase.org/gamuts/store/docs/GAMUTS_Supplemental_table%202_footprints_4_181220.pdf

Originally presented at the SSIEM 2023 Annual Symposium.Neuronopathic Gaucher disease: Rare in the West, common in the EastOzlem Goker-Alpan, Margarita M. Ivanovahttps://doi.org/10.1002/jimd.12749

Dr Melanie Gillingham, PhD, RD, joins the podcast to discuss eye disease in LCHADD and changes in outcomes following early or late diagnosis. Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathyMelanie B. Gillingham, et alhttps://doi.org/10.1002/jimd.12738

Professor Corrado Angelini joins Eva Morava to discuss the footprints of metabolic myopathies, why they are so common and when they should be suspected. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2022.09.004Find IMDs associated with epilepsies at: http://www.iembase.org/gamuts/store/docs/Footprints_myopathies_table%20151022.pdf

Concluding our limited series related to the SSIEM 2024 meeting in Porto. We reflect on Day 3 and modelling disease through organoids, nursing in IMD investigation of hypoglycaemia. We also hear more about dolichol metabolism and George Komrower.

Thoughts on the second day of SSIEM 2024 annual symposium and a little preview of day 3.

A look back on the first day of the SSIEM 2024 Annual Symposium and a preview of Day 2 with Rodrigo Starosta co-hosting.

The first of a series of podcasts accompanying the 2024 annual symposium of the SSIEM 2024. In this episode Dr Dulce Quelhas reflects on her plans for the meeting and just how long it has been gestating. Stay tuned for daily content.

Professor Judy Fridovich-Keil returns to the podcast to explain her work to illustrate whether the phenotype of galactosemia is related to GALT activity or galactose metabolism. Her group have been working with plant enzymes in fruit flies. Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adult climbing deficit in a GALT-null D. melanogaster model of classic galactosemiaJennifer M. I. Daenzer, et alhttps://doi.org/10.1002/jimd.12774

Professors Fréd Vaz and Ronald Wanders present an entertaining and informative overview of fatty acid homeostasis and explain why the catabolic and anabolic processes cannot be considered separately.Disorders of fatty acid homeostasisFrédéric M. Vaz, et al https://doi.org/10.1002/jimd.12734

Dr Annet Bosch describes three cases where young adults developed worsening neurological symptoms after a change in diet. Initially confused with Guillan-Barré Syndrome, this treatable condition may be hard to diagnose but devastating to miss. Find full details here: https://doi.org/10.1002/jmd2.12427

Dr Irena Muffels is joined by Professor Eva Morava to discuss insights into heterozygous DHDDS variants, an autosomal dominant IMD that appears to impact on multiple different metabolic pathways. Assessing age of onset and clinical symptoms over time in patients with heterozygous pathogenic DHDDS variantsI. J. J. Muffels, et alhttps://doi.org/10.1002/jimd.12769

Professor Phillip Pearl joins Eva Morava to discuss the footprints of metabolic epilepsies and a very brief introduction to the intertwined nature of music and neurology. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2023.107690Find IMDs associated with epilepsies at: http://iembase.org/gamuts/store/docs/IMDs_presenting_with_epilepsies_010124.pdf

Dr Henry Lee joins the podcast to discuss the challenges of developing gene therapies for inherited disorders of neurotransmission and shares the progress that his group has made with SSADH deficiency. Gene replacement therapies for inherited disorders of neurotransmission: Current progress in succinic semialdehyde dehydrogenase deficiencyHenry H. C. Lee, et alhttps://doi.org/10.1002/jimd.12735

Dr Tom Hartl discusses his group's work with a mouse model that knocks out both GALT and GALK and the insights that this provides into classic galactosemia.Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemiaLinley Mangini, et alhttps://doi.org/10.1002/jmd2.12438

Marjorie Dixon and Annemiek van Wegberg join guest host Curtis Coughlin II to complete the treatment puzzle in pyridoxine dependent epilepsy and explain the role and practicalities of lysine restriction in PDE.Dietary management for pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency, a follow-on from the international consortium guidelinesMarjorie Dixon, et alhttps://doi.org/10.1002/jmd2.12418

Nenad Blau hosts Professor David Cassiman as he explains when to consider a metabolic differential in pediatric and adult liver disease. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2019.04.002Find liver disorders associated with IMDS at: http://iembase.org/gamuts/store/docs/Liver_disorders_in_inherited_metabolic_disorders.pdf

In the latest shortcast, Inez Bosnyak describes a case of ALG1-CDG presenting without an abnormal isoelectric focusing pattern. Normal transferrin glycosylation does not rule out severe ALG1 deficiencyInez Bosnyak, et alhttps://doi.org/10.1002/jmd2.12415

Speech & neural oscillation in classic galactosemia by Journal of Inherited Metabolic Disease

Alexandre Nguyen and Manuel Schiff share the story of two siblings with severe haemolytic anaemia developing in previously well controlled methionine synthase reductase deficiency.Late-onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose escalation?Alexandre Nguyen, et alhttps://doi.org/10.1002/jmd2.12422

Dr Fanny Mochel returns to the podcast to answer the question, "What can pediatricians learn from adult inherited metabolic diseases?".What can pediatricians learn from adult inherited metabolic diseases?Fanny Mochelhttps://doi.org/10.1002/jimd.12729

Dr Vykunta Raju K N, Professor of Paediatric Neurology discusses a child presenting with IUGR, microcephaly, cataracts, developmental delay, seizures, and cerebral atrophy.L-Serine Biosynthesis Defect: A Treatable Condition Masquerading as TORCH InfectionVykuntaraju K. Gowda et alhttps://link.springer.com/article/10.1007/s12098-024-05181-3

Eva Morava discusses the creation of the IEMbase with Nenad Blau before the pair welcome Gabriella Horvath to discuss metabolic mimics of cerebral palsy in the first episode of the footprints series. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2021.03.008Find all the metabolic mimics of CP at http://iembase.org/gamuts/store/docs/Metabolic_mimics_of_cerebral_palsy.pdf

Dr Maja Risager Nielsen and Dr François Feillet discuss pregnancy in PKU and two different papers looking at the outcomes in pregnancies with and without BH4 treatment. The impact of phenylalanine levels during pregnancy on birth weight and later development in children born to women with phenylketonuriaMaja Risager Nielsen, et alhttps://doi.org/10.1002/jimd.12600Efficacy and safety of sapropterin before and during pregnancy: Final analysis of the Kuvan® Adult Maternal Paediatric European Registry (KAMPER) maternal and Phenylketonuria Developmental Outcomes and Safety (PKUDOS) PKU-MOMs sub-registriesFrançois Feillet, et alhttps://doi.org/10.1002/jimd.12724

When might acute liver failure have a metabolic cause? Dr Robert Hegarty tries to answer this question and more following his recent review article on Genetic aetiologies of acute liver failure.Genetic aetiologies of acute liver failureRobert Hegarty, Richard J. Thompsonhttps://doi.org/10.1002/jimd.12733

Dr Mariko Bennett and Dr Laura Adang discuss the precarious balance between a protective and a destructive immune response, as is seen in inborn errors in nucleotide metabolism. Our discussion focuses on the most common of these disorders: Aicardi Goutières syndrome (AGS). Sadly, despite the many gains in understanding about AGS, there remain many gaps in our understanding of this condition.Nucleotide metabolism, leukodystrophies, and CNS pathologyFrancesco Gavazzi, et alhttps://doi.org/10.1002/jimd.12721

Dr Gustavo Spolador discusses the paucity of data around palliative care in Inherited Metabolic Disease and some of his own observations in a Brazilian quaternary hospital.Pediatric palliative care for metabolic diseases: 20-year epidemiological survey of outpatients at a Brazilian quaternary hospitalGustavo Marquezani Spolador, et alhttps://doi.org/10.1002/jmd2.12417

This episode brings together two popular podcast topics, pregnancy and urea cycle disorders. Dr Margreet Wagenmakers and Dr Karolina Stepien share recent insights from a literature review and international survey exploring the experiences of mothers with urea cycle disorders. The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international surveyKarolina M. Stepien, et alhttps://doi.org/10.1002/jimd.12695

Mel McSweeney and Dr Mildrid Yeo briefly outline the approach to urea cycle disorder management and the Gt Ormond Street experience using glycerol phenylbutyrate as a nitrogen scavenger. Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centreMildrid Yeo, et alhttps://doi.org/10.1002/jmd2.12386

The podcast returns to the subject of gene therapy, with Julien Baruteau, Nicola Brunetti-Pierri, and Paul Gissen discussing the potential of liver directed therapies with an emphasis on Wilson disease, Crigler-Najjar syndrome and PKU.Liver-directed gene therapy for inherited metabolic diseasesJulien Baruteau, Nicola Brunetti-Pierri, Paul Gissenhttps://doi.org/10.1002/jimd.12709

Dr Maren Thiel, Chair of the German speaking self-help group for fatty oxidation disorders, presents work completed with the Freiburg metabolic team looking at psychosocial issues and coping strategies in families affected by LC-FAOD.Psychosocial issues and coping strategies in families affected by long-chain fatty acid oxidation disordersMaren Thiel, et alhttps://doi.org/10.1002/jmd2.12402

Listener feedback link: https://form.jotform.com/240459204544050Kunwar Jung-KC and Alba Tristán-Noguero discuss tyrosine hydroxylase deficiency and explain how the tyrosine hyodroxylase cofactor, BH4, has shown early therapeutic potential in human neurons and a knock-in mouse model. Tetrahydrobiopterin (BH4) treatment stabilizes tyrosine hydroxylase: Rescue of tyrosine hydroxylase deficiency phenotypes in human neurons and in a knock-in mouse modelKunwar Jung-KC, Alba Tristán-Noguero, et alhttps://doi.org/10.1002/jimd.12702

Dr Hiroki Hanafusa presents the unusual case of a woman who was initially diagnosed with Fanconi Syndrome and later found to have Lysinuric Protein Intolerance.Lysinuric protein intolerance exhibiting renal tubular acidosis/Fanconi syndrome in a Japanese womanHiroaki Hanafusa, et alhttps://doi.org/10.1002/jmd2.12392

A superlative trio, Dr Machteld Oud, Dr Clara van Karnebeek and Dr Saskia Wortmann join the podcast to explain the importance of diagnostics, why all exomes aren't equal and just how should you proceed after a 'negative' exome.How to proceed after “negative” exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniquesSaskia B. Wortmann, et alhttps://doi.org/10.1002/jimd.12507

Merel Hermans describes her work reviewing neuropsychological stability in adults with classical galactosemia.Neuropsychological stability in classical galactosemia: A pilot study in 10 adult patientsMerel E. Hermans, et alhttps://doi.org/10.1002/jmd2.12410

Returning guests, Nina Stolwijk and Dr Carla Hollak, and their colleague Dr Annet Bosch, try to untangle the tricky subject of regulation in nutritional products used as therapies in IMD. They also present a framework for when a food should be considered a medicine. Food or medicine? A European regulatory perspective on nutritional therapy products to treat inborn errors of metabolismN. N. Stolwijk, et alhttps://doi.org/10.1002/jimd.12677

Shelby Mills on behalf of the UTH Medical Genetics Team, invites you to consider three mystery cases serving to hi-light some common, and some less common, presenting features for a treatable inherited metabolic disease.Arginase deficiency masked by cerebral palsy and coagulopathy—Three varied presentations of Latin American originShelby L. Mills, et alhttps://doi.org/10.1002/jmd2.12397

Dr Sonam Gurung and Dr Julien Baruteau discuss movement disorders in Arginosuccinic aciduria and explain how recent work with mRNA therapy shows potential as a treatment in this condition.The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduriaGurung et alhttps://doi.org/10.1002/jimd.12691mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduriaGurung et alhttps://doi.org/10.1126/scitranslmed.adh1334

Dr Malak Alghamdi unravels the mystery of a 32-year-old woman with a history of recurrent miscarriage and early neonatal death with congenital anomalies. Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal womanMalak Ali Alghamdi, et al https://doi.org/10.1002/jmd2.12384

In this podcast, Dr Roshni Vara discusses the experience of a single paediatric liver centre with children whose liver failure arose due to a mitochondrial DNA depletion syndrome.Hepatic presentations of mitochondrial DNA depletion syndrome in children: A single tertiary liver centre experienceR. Vara, et alhttps://doi.org/10.1002/jimd.12633

Professor Jayesh Sheth shares 20 years of insights on diagnosing adult onset lysosomal storage disorders at a tertiary genetic centre in India.Lysosomal storage disorders identified in adult population from India: Experience of a tertiary genetic centre and review of literatureJayesh Sheth, et alhttps://doi.org/10.1002/jmd2.12407

Dr David Bick, Dr Jim Bonham MBE and Henrietta Hopkins re-create a panel from the SSIEM Annual Meeting in 2022 to discuss the use of whole genome sequencing in NBS, asking "are we entering a new era of screening?"Genomic newborn screening: Are we entering a new era of screening?Ute Spiekerkoetter, et alhttps://doi.org/10.1002/jimd.12650

Dr Sander Houten discusses a child with hyperlysinemia diagnosed via newborn screening and whether this reflects a disease or just a metabolic perturbation. This distinction is relevant as inducing this state may be a treatment option in GA1 or pyridoxine dependent epilepsy. A case of hyperlysinemia identified by urine newborn screeningMehdi Yeganeh, et alhttps://doi.org/10.1002/jmd2.12399

The Journal of Inherited Metabolic Disease Editorial Committee come together to talk about the direction of metabolic medicine, the dangers and potential of AI, impact factors, reviewing papers and their publication hopes for 2024. There's also a little metabolic quiz, allowing you to pit your wits against the committee. Featuring: Shamima Rahman, Matthias Baumgartner, Verena Peters, Marc Patterson, Johannes Zschocke and Sean Froese.Quo vadis now: Beyond genomics to an era of personalised medicineShamima Rahman, et alhttps://doi.org/10.1002/jimd.12487Risk and potential of ChatGPT in scientific publishingVerena Peters, et alhttps://doi.org/10.1002/jimd.12666

Blood spots are integral to disease monitoring in PKU, however, there are concerns regarding correlation between capillary and plasma levels and discrepancies arising based on sampling quality and storage. Dr Rachel Carling explains how a volumetric blood collection device presents a cost effective way to improve consistency and reduce rejected samples. Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devicesRachel S. Carling, et alhttps://doi.org/10.1002/jmd2.12398

In our latest podcast, Antonia Ribes, Frederic Tort, and Gerard Muñoz-Pujol discuss CRISPR/Cas9 based technique for the validation of genetic variants requiring just the genetic data. CRISPR/Cas9-based functional genomics strategy to decipher the pathogenicity of genetic variants in inherited metabolic disordersGerard Muñoz-Pujol, et alhttps://doi.org/10.1002/jimd.12681

In the latest Shortcast, Jared J. Druss and Professors Nancy Potter and Judy Fridovich-Keil discuss grip strength in galactosemia (and how competitive boys can bias study results).Grip strength in patients with galactosemia and in a galactose-1-phosphate uridylyltransferase (GALT)-null rat modelJared J. Druss, et alhttps://doi.org/10.1002/jimd.12684

Dr Dwight Koeberl joins the podcast to provide some background to gene therapies in Glycogen Storage Disorders, hi-light some ongoing studies and explain why we owe at least some of our knowledge to a menagerie of animal models. Gene therapy for glycogen storage diseasesDwight D. Koeberl, et alhttps://doi.org/10.1002/jimd.12654

Dr Will Heath describes insights form screening data derived from 19 patients enrolled in a phase 1 study in late-onset Pompe disease.Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapyWilliam B. Hannah, et alhttps://doi.org/10.1002/jmd2.12391

In an ensemble piece, Dr Saskia Wortmann, Dr Hud Freeze, and Dr Santiago Ramón-Maiques discuss CAD deficiency and the challenge of finding new ways to validate genetic variants when pathogenicity seems uncertain. Beyond genetics: Deciphering the impact of missense variants in CAD deficiencyFrancisco del Caño-Ochoa, et alhttps://doi.org/10.1002/jimd.12667

Dr Kaustuv Bhattacharya explains the insights of his team into the diagnosis and management of a cohort of children with McArdle Syndrome and challenges some of the conceptions around this disease. Diagnosis and management of children with McArdle Syndrome (GSD V) in New South WalesLouisa Adams, et alhttps://doi.org/10.1002/jmd2.12389

Dr Rodrigo Starosta describes the management of a challenging presentation of PIGO-CDG and discusses insights into this rare GPI-anchor disorder. PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerationsRodrigo Tzovenos Starosta, et alhttps://doi.org/10.1002/jmd2.12396

It's a 2-for-1 podcast as Dr Mattias Lissing of the Karolinska Institute joins us to discuss two recent papers looking at cancer risk, comorbidity and mortality in the acute porphyrias.Risk for incident comorbidities, nonhepatic cancer and mortality in acute hepatic porphyria: A matched cohort study in 1244 individualsMattias Lissing, et alhttps://doi.org/10.1002/jimd.12583Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case–control study of 188 patientsMattias Lissing, et alhttps://doi.org/10.1002/jimd.12676

Dr Markey McNutt of UT South Western describes a patient presenting with post-partum ataxia and confusion and just when you think you know the answer there's an extra mystery at the end. Read the paper here:https://doi.org/10.1002/jmd2.12388

Dr Claire Horgan discusses the first year of offering gene therapy to patients with metachromatic leukodystrophy (MLD) in the UK. When given in a timely fashion the impact is incredible but large numbers of children remain ineligible for treatment. A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie aheadClaire Horgan, et alhttps://doi.org/10.1002/jmd2.12378

In this podcast, Dr Kristen Skvorak discusses the development and testing of a new oral enzyme for the treatment of Maple Syrup Urine Disease. Oral enzyme therapy for maple syrup urine disease (MSUD) suppresses plasma leucine levels in intermediate MSUD mice and healthy nonhuman primatesKristen Skvorak, et alhttps://doi.org/10.1002/jimd.12662

Enzyme Replacement Therapy (ERT) has changed the course of several lysosomal storage disorders but regular, intravenous administration is not without its issues. In this latest Shortcast, Dr Paulina Dabrowska-Schlepp describes her group's work to develop subcutaneous ERT for Fabry Disease.Comparison of efficacy between subcutaneous and intravenous application of moss-aGal in the mouse model of Fabry diseasePaulina Dabrowska-Schlepp, et alhttps://doi.org/10.1002/jmd2.12393

Dr Luisa Averdunk of the University Children's Hospital in Düsseldorf discusses the investigation of a 2-year-old presenting with acute episodes of dystonia and symmetrical basal ganglia abnormalities. Will you unravel this metabolic mystery before all is revealed?See the associated image and read the full report here:https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12680

In our latest podcast we welcome Simon Waddington, Professor in Gene Transfer Technology at the EGA Institute for Women's Health. Professor Waddington discusses the development of fetal gene therapy and why it might be desirable to deliver gene therapy to the unborn child.Fetal gene therapySimon N. Waddington, et alhttps://doi.org/10.1002/jimd.12659

Dr Oliver Heath describes a new patient with CADDS who developed pancreatic exocrine deficiency and interstitial lung disease. Interstitial lung disease and pancreatic exocrine insufficiency in CADDS: Phenotypic expansion and literature reviewOliver Heath, et alhttps://doi.org/10.1002/jmd2.12390

Professor Ute Spiekerkoetter co-hosts a special episode of the podcast, compiled to accompany the SSIEM 2022 themed issue from September 2023 and look back on a wonderful meeting hosted in Freiburg the year before. This episode features three different papers and you jump straight to these at the following locations:6 min 25 sec: Dr Carla Hollak, Noa Rosenburg and Nina Stolwijk discuss public-private partnerships in drug development27 min 10 sec: Professor Martina Huemer explains how we should all be using patient reported outcome measures in our work37 min 16 sec: Kiera Batten explains the role of exercise and exercise prescription in inherited metabolic diseaseDevelopment of medicines for rare diseases and inborn errors of metabolism: Toward novel public–private partnershipsNoa Rosenberg, et alhttps://doi.org/10.1002/jimd.12605Measuring what matters: Why and how to include patient reported outcomes in clinical care and research on inborn errors of metabolismMartina Huemer, et alhttps://doi.org/10.1002/jimd.12622Exercise testing and prescription in patients with inborn errors of muscle energy metabolismKiera Batten, et alhttps://doi.org/10.1002/jimd.12644

Dr Julien Barateau joins the podcast to look back at the history of gene therapy research in Urea Cycle Disorders, and discuss the future of genomic therapies in this group of conditions with a high unmet need.Gene therapy for urea cycle defects: An update from historical perspectives to future prospectsClaire Duff, et alhttps://doi.org/10.1002/jimd.12609

Dr Sander Houten of the Icahn School of Medicine returns to the podcast to explain his work exploring opportunities for substrate reduction therapy in disorders of valine and isoleucine metabolism.Acyl-CoA dehydrogenase substrate promiscuity: Challenges and opportunities for development of substrate reduction therapy in disorders of valine and isoleucine metabolismSander M. Houten, et alhttps://doi.org/10.1002/jimd.12642

In a 'short' Shortcast, Dr Julien Baruteau introduces his Report of two infantile-onset cases of remethylation defects and their response to treatment. Prolonged respiratory failure responds to conventional therapy in isolated homocysteine remethylation defectsAbigail Whitehouse, et alhttps://doi.org/10.1002/jmd2.12375

Dr Itay Latzer, from Boston Children's Hospital, joins the podcast to discuss the development and utility of a clinical severity scoring system in the ultra-rare disease SSADHD.Establishment and validation of a clinical severity scoring system for succinic semialdehyde dehydrogenase deficiencyItay Tokatly Latzer, et alhttps://doi.org/10.1002/jimd.12635

Dr Emma Glamuzina of the National Metabolic Service in New Zealand, describes a neonatal presentation of CARS2- related mitochondrial disease and the diagnostic challenges this brought in a pre-exome/genome era. Severe neonatal onset neuroregression with paroxysmal dystonia and apnoea: Expanding the phenotypic and genotypic spectrum of CARS2-related mitochondrial diseaseJessie Poquérusse, et alhttps://doi.org/10.1002/jmd2.12360

Dr Daphne Vassiliou joins the podcast to discuss past concerns about pregnancy in porphyria and how more data has reassured regarding safety and hi-lighted areas for increased vigilance.

Maternal and fetal outcomes in acute hepatic porphyria: A Swedish National Cohort Study Ängla Mantel, et al https://doi.org/10.1002/jimd.12616

Nicola Brunetti-Pierri of the Telethon Institute of Genetics and Medicine joins the podcast to discuss his recent review looking at the various gene therapy approaches in the mucopolysaccharidoses along with their strengths and limitations.

Gene therapies for mucopolysaccharidoses Alessandro Rossi and Nicola Brunetti-Pierri https://doi.org/10.1002/jimd.12626

Dr Isabelle Adant follows up on a recent review on ATP7A with the case of a neonate presenting with occipital horn syndrome.

Neonatal presentation of occipital horn syndrome caused by a ATP7A missense variant Isabelle Adant, et al https://doi.org/10.1002/jimd.12621

Professor Judy Fridovich-Keil returns to the podcast to explain gaps in research data around the S135L variant in classic galactosemia and why current data sets may not not truly reflect the international experience of galactosemia.

A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT Quinton S. Katler, et al https://doi.org/10.1002/jimd.12556

Racial and ethnic diversity of classic and clinical variant galactosemia in the United States Stettner et al https://doi.org/10.1016/j.ymgme.2023.107542

Professor Ranganath discusses his observations around the increased incidence of Parkinson's disease in Alkaptonuria and shares his thoughts on the possible pathophysiology.

Dr Jayesh Sheth discusses two patients diagnosed with MLD following milder presentations, both related to novel missense variants in the PSAP gene.

Late infantile and adult-onset metachromatic leukodystrophy due to novel missense variants in the PSAP gene: Case report from India Jayesh Sheth, et al https://doi.org/10.1002/jmd2.12374

Dr Manuel Schiff and Dr Clément Pontoizeau join us for the first JIMD Podcast on Maple Syrup Urine Disease, hi-lighting their recent successes treating a Bckdhb knock-out mouse model using gene therapy.

Successful treatment of severe MSUD in Bckdhb−/− mice with neonatal AAV gene therapy Clément Pontoizeau, et al https://doi.org/10.1002/jimd.12604

Professor Sverre Sandberg joins the podcast to discuss recent work looking to establish key terms and definitions in the acute porphyrias, and explains how this will ultimately help bring forward treatment and research.EPNet website: http://porphyria.euKey Terms and Definitions in Acute Porphyrias: Results of an International Delphi Consensus Led by the European Porphyria NetworkPenelope E. Stein, et alhttps://doi.org/10.1002/jimd.12612

Dr Silvia Radenkovic, Professor Eva Morava and Professor Kent Lai join the podcast to discuss recent insights that may enable prognostication in PGM1-CDG, and a promising gene therapy study that could address the cardiomyopathy that remains untreated by Galactose therapy. The role of PGM1 isoform 2 in PGM1-CDG: One step closer to genotype–phenotype correlation?Silvia Radenkovic, et alhttps://doi.org/10.1002/jimd.12601Interested listeners may want to read gene therapy paper discussed herein:https://doi.org/10.1016/j.trsl.2023.01.004

Dr Marne Hagemeijer joins the podcast to explain how mass spectrometry could simplify the approach to screening urine samples for evidence of Lysosomal Storage Disorders.Analysis of urinary oligosaccharide excretion patterns by UHPLC/HRAM mass spectrometry for screening of lysosomal storage disordersMarne C. Hagemeijer, et alhttps://doi.org/10.1002/jimd.12597

Professor Michel Polak reports success using a specialist preparation of oral glibenclamide in the management of neonatal diabetes in an extreme preterm infant subsequently found to have a KCNJ11 gene variant. Early treatment of neonatal diabetes with oral glibenclamide in an extremely preterm infantAlfonso Galderisi, et alhttps://doi.org/10.1002/jmd2.12358

Dr Irene Chang and Dr An Dang Do explain how an infant presenting with cholestasis and liver disease kept them guessing, and how the abnormal biochemical findings gave them new insights into other conditions. Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylationAn N. Dang Do, et alhttps://doi.org/10.1002/jimd.12595

Dr RaeLynn Forsyth describes a pioneering patient who contributed to the evolution and understanding or Urea Cycle Disorder treatments throughout her life. The remarkable journey of one female individual with ornithine transcarbamylase deficiency diagnosed post-mortemRaeLynn Forsyth, et alhttps://doi.org/10.1002/jmd2.12361

Dr Hana Alharbi, Dr Earnest James Paul Daniel, and Dr Andrew C. Edmondson join the podcast to talk about ATP6AP1-CDG and the potential for fractionated plasma N-glycan profiling.Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic associationHana Alharbi, et alhttps://doi.org/10.1002/jimd.12589

Dr Caoimhe Howard presents her teams' report of a young boy with MTFMT-related mitochondrial disease. Autonomic instability, arrhythmia and visual impairment in a new presentation of MTFMT-related mitochondrial diseaseCaoimhe Howard, et alhttps://doi.org/10.1002/jmd2.12355

This podcast, and the first paper, are dedicated to the memory of Dr. Nassim Shahrzad, an accomplished scientist with a bright future who was taken from her family, friends and colleagues much too soon. May the memory of her warm smile, collegial nature and devotion to her family serve as a source of comfort and inspiration to all those who knew her.In this podcast we return to TANGO2-deficiency disorder to hear from Dr Michael Sacher, Dr Christina Miyake and Dr Samuel Mackenzie, on how research in a drosophila disease model correlates with insights from natural history studies on the role for B-complex vitamins in TDD.Vitamin B5, a coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in Drosophila and human cellsParia Asadi, et alhttps://doi.org/10.1002/jimd.12579B-complex vitamins for patients with TANGO2-deficiency disorderSarah E. Sandkuhler, et alhttps://doi.org/10.1002/jimd.12585

Dr Nour Elkhateeb describes his group's experience managing a patient with homocystinuria who developed paracetamol toxicity and was subsequently treated with N-acetylcysteine.Paracetamol toxicity in classic homocystinuria: Effect of N-acetylcysteine on total homocysteineNour Elkhateeb, et alhttps://doi.org/10.1002/jmd2.12363

Dr Sean Froese returns to the podcast alongside Professor Wyatt Yue to discuss cobalamin, crystallography and consuming raw liver. The complex machinery of human cobalamin metabolismThomas J. McCorvie, et alhttps://doi.org/10.1002/jimd.12593

Merel Post discusses her group's work to describe 6 individuals with MOGS-CDG and the utility of a tetrasaccharide biomarker for confirming diagnosis and possibly for treatment monitoring in future. MOGS-CDG: Quantitative analysis of the diagnostic Glc3Man tetrasaccharide and clinical spectrum of six new casesMerel A. Post, et alhttps://doi.org/10.1002/jimd.12588

Dr Patrick Forny and Dr Nikolas Boy join the podcast to discuss their recent paper that considers how guideline development feeds into research targets and how new research is integrated into guidelines.How guideline development has informed clinical research for organic acidurias (et vice versa)Patrick Forny, et alhttps://doi.org/10.1002/jimd.12586

Dr Ruqaiah Altassan describes the successful heart transplantation in a child with PGM1-CDG. Successful heart transplantation in an infant with phosphoglucomutase 1 deficiency (PGM1-CDG)Ruqaiah Altassan, et alhttps://doi.org/10.1002/jmd2.12350You may also be interested in:AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase I deficiency (PGM1-CDG). Balakrishnan et alhttps://www.sciencedirect.com/science/article/abs/pii/S193152442300004X?via%3Dihub

Dr Milad Khedr, Dr Nick Sireau and Professor Ranganath discuss a decade of success for the UK National Alkaptonuria Centre and how close integration with the AKU Society works to provide better care for all patients.First decade anniversary of the United Kingdom National Alkaptonuria CentreMilad Khedr, et alhttps://doi.org/10.1002/jmd2.12340

Dr Sean Froese and Dr Charlotte Ramon join the podcast to discuss the different hypotheses around cellular damage in MMA, and new insights obtained through cellular and computational models. Cellular and computational models reveal environmental and metabolic interactions in MMUT-type methylmalonic aciduriaCharlotte Ramon, et alhttps://doi.org/10.1002/jimd.12575

Dr Suzanne Jackowski shares the fruits of a career looking at Co-enzyme A and the results of recent work looking at a promising molecule in a propionic acidemia mouse model. Relief of CoA sequestration and restoration of mitochondrial function in a mouse model of propionic acidemiaChitra Subramanian, et alhttps://doi.org/10.1002/jimd.12570

Dr Richard Steet discusses his group's recent work describing compound heterozygous variants within two conserved sialyltransferase motifs of ST3GAL5 leading to GM3 synthase deficiency.Compound heterozygous variants within two conserved sialyltransferase motifs of ST3GAL5 cause GM3 synthase deficiencyNatasha Rudy, et alhttps://doi.org/10.1002/jmd2.12353

Ashley Hertzog returns to the shortcast to discuss how ascertainment bias may hinder the assessment of clinical phenotype in patients with 3-Methylglutaconyl-CoA hydratase deficiency.3-Methylglutaconyl-CoA hydratase deficiency: When ascertainment bias confounds a biochemical diagnosisAshley Hertzog, et alhttps://doi.org/10.1002/jmd2.12332

In a bumper episode, Professor Shamima Rahman helps to host Dr Rhys Thomas, Lyndsey Butterworth, Dr Amy Hunter and Russell Wheeler in a discussion around the recent Priority Setting Partnership in Primary Mitochondrial Disease.Research priorities for mitochondrial disorders: Current landscape and patient and professional viewsRhys H. Thomas, et alhttps://doi.org/10.1002/jimd.12521

Dr Spyros Batzios describes a patient diagnosed with hyperphosphatasia with mental retardation syndrome 3 (also known as Mabry Syndrome) and reports on novel findings of CSF abnormalities and response to treatment with pyridoxine and folinic acid.Hyperphosphatasia with mental retardation syndrome 3: Cerebrospinal fluid abnormalities and correction with pyridoxine and Folinic acidMartina Messina, et alhttps://doi.org/10.1002/jmd2.12347

Dr Nikolas Boy joins the podcast to discuss the recently published third revision of the guidelines for the diagnosis and management of Glutaric Aciduria Type 1. Dr Boy explains what has changed, what has stayed the same, and why these changes have happened. Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revisionNikolas Boy, et alhttps://doi.org/10.1002/jimd.12566

Kristen Wheeden of the United Porphyrias Association joins as podcast co-host to ask David Cassiman, Pieter Vermeersch and Amy Dickey about improving diagnostics in porphyria and the outcomes of the EXPLORE B and POWER surveys exploring quality of life. Development and validation of diagnostic algorithms for the laboratory diagnosis of porphyriasStefanie Lefever, et alhttps://doi.org/10.1002/jimd.12545EXPLORE B: A prospective, long-term natural history study of patients with acute hepatic porphyria with chronic symptomsDavid Cassiman, et alhttps://doi.org/10.1002/jimd.12551Quantifying the impact of symptomatic acute hepatic porphyria on well-being via patient-reported outcomes: Results from the Porphyria Worldwide Patient Experience Research (POWER) studyAmy Dickey, et alhttps://doi.org/10.1002/jmd2.12343

Dr Eva Hoytema van Konijnenburg describes the case of a patient with mevalonate kinase deficiency presenting solely with neurological symptoms and without an inflammatory component.Isolated neurological presentations of mevalonate kinase deficiencyEva Hoytema van Konijnenburg, et al https://doi.org/10.1002/jmd2.12348

Tessa Peters and Dr Leticia Pías-Peleteiro join the podcast to discuss GLUT1 deficiency syndrome and recent insights around the potential for new biomarkers.Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficitTessa M. A. Peters, et alhttps://doi.org/10.1002/jimd.12554

Jenny McNulty describes the management of a successful pregnancy in a woman with long-chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHADD).Management of pregnancy in a patient with long-chain 3-hydroxyacyl CoA dehydrogenase deficiencyLoai A. Shakerdi, et alhttps://doi.org/10.1002/jmd2.12284

Dr Mary Riedy discuss an infant with infantile-onset Pompe disease and the challenges of an unusual neutropenia phenotype. Infantile-onset Pompe disease with neutropenia: Treatment decisions in the face of a unique phenotypeMary Riedy, et alhttps://doi.org/10.1002/jmd2.12337

Dr Stephan Kemp returns to the podcast to discuss the recent pilot for sex-specific newborn screen for X-linked adrenoleucodystrophy in the Netherlands. The discussion includes the screening pathway, the decision to make it sex specific and a review of the pilot findings. Sex-specific newborn screening for X-linked adrenoleukodystrophyMonique Albersen, et alhttps://doi.org/10.1002/jimd.12571

Dr Mildrid Yeo discusses a single centre's experience of transitioning UCD children from Sodium benzoate to glycerol phenylbutyrate. Direct replacement of oral sodium benzoate with glycerol phenylbutyrate in children with urea cycle disordersMildrid Yeo, et alhttps://doi.org/10.1002/jmd2.12274

Maria Veiga-da-Cunha, Claudia Soler-Alfonso and Sarah Grünert join the podcast to talk about Empagliflozin, a repurposed drug with impressive efficacy in GSD 1b and G6PC3 deficiency.Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: Impact of a mutation in SGLT5Cécile Boulanger, et alhttps://doi.org/10.1002/jimd.12509Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatmentEran Tallis, et alhttps://doi.org/10.1002/jmd2.12304Two successful pregnancies and first use of empagliflozin during pregnancy in glycogen storage disease type IbSarah Catharina Grünert, et alhttps://doi.org/10.1002/jmd2.12295

Lydia Healy, Meabh O'Shea and Professor Ahmad Ardeshir Monavari report the Irish experience with GA1, both before and after the introduction of new born screening for the condition. Glutaric aciduria type 1: Diagnosis, clinical features and long-term outcome in a large cohort of 34 Irish patientsLydia Healy, et alhttps://doi.org/10.1002/jmd2.12302

Dr Mary Kay Koenig describes the use of elamipretide in three children with different mitochondrial disorders. Her group's work provides dosing parameters for the use of elamipretide in patients <12 years of age with mitochondrial diseases caused by pathogenic variants that impair membrane phospholipid remodelling.Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseasesMary Kay Koenig, et alhttps://doi.org/10.1002/jmd2.12335

In this podcast, Dr Chuck Venditti of the National Human Genome Research Institute, discusses his passion for MMA, the role of screening and the mechanisms behind different types of genomic therapy. Treatment of metabolic disorders using genomic technologies: Lessons from methylmalonic acidemiaLeah E. Venturoni and Charles P. Vendittihttps://doi.org/10.1002/jimd.12534

Transcription (RNA) of the genes that regulate the heme-synthesis pathway in the liver is modified in a patient with acute intermittent porphyria.Transcriptomic study in explanted liver from a patient with acute intermittent porphyriaJordi To-Figueras, et alhttps://doi.org/10.1002/jmd2.12329

Chiel de Bode explains that orofacial abnormalities are present in all types of mucopolysaccharidosis, mucolipidosis II, and III, and therefore evaluation of orofacial health should be part of routine clinical care in these patients.Orofacial abnormalities in mucopolysaccharidosis and mucolipidosis type II and III: A systematic reviewChiel J. de Bode, et alhttps://doi.org/10.1002/jmd2.12331

Dr Daniah Albokhari and Dr Andrew Edmondson speak to the podcast about 7 new patients with ALG8-CDG and discuss how their knowledge of the condition helps formulate clinical guidance in this ultra-rare disease.

ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines Daniah Albokhari, et al https://doi.org/10.1002/jimd.12527

Maryam Ziadlou presents her work documenting an alternative approach to achieving good metabolic control in a case series of MSUD patients.

Alternative sources of valine and isoleucine for prompt reduction of plasma leucine in maple syrup urine disease patients: A case series Maryam Ziadlou, and Anita MacDonald https://doi.org/10.1002/jmd2.12327

In this Shortcast, Dr Arthavan Selvanathan of the Queensland Lifespan Metabolic Medicine Service, discusses his team's work: N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report

N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report Arthavan Selvanathan, et al

https://doi.org/10.1002/jmd2.12318

Dr Lisette Koens joins the podcast to discuss her work that seeks to address some of the knowledge gaps that exist around eye movement disorders in late onset IMD.

Eye movement disorders in inborn errors of metabolism: A quantitative analysis of 37 patients Lisette H. Koens, et al https://doi.org/10.1002/jimd.12533

Dr Katrin Õunap presents her group's recent work, the prevalence of inherited metabolic disorders in the Estonian population over 30 years: A significant increase during the study period.

The prevalence of inherited metabolic disorders in Estonian population over 30 years: A significant increase during study period Elis Tiivoja, et al https://doi.org/10.1002/jmd2.12325

Dr Shanti Balasubramaniam and her team report a further case of a pathogenic, heterozygous, de novo variant in CTBP1 and discusses muscle biopsy findings in this disorder.

Mitochondrial respiratory chain dysfunction in a patient with a heterozygous de novo CTBP1 variant Wui-Kwan Wong, et al https://doi.org/10.1002/jmd2.12326

Expanding on their recent editorial, Shamima Rahman, Eva Morava and Tamas Kozicz discuss the doxycycline paradox and why a medication previously thought to be toxic might present an avenue for treatment in some primary mitochondrial disorders.

The doxycycline paradox in primary mitochondrial diseases Tamas Kozicz, Shamima Rahman, and Eva Morava https://doi.org/10.1002/jimd.12531

Dr Sandra Sirrs returns to the podcast to discuss her work developing training competencies for adult metabolic medicine.

Training competencies in adult metabolic medicine: A survey of working adult metabolic medicine physicians Sandra Sirrs, et al https://doi.org/10.1002/jmd2.12312

The right tool for the job—Fit for purpose training programs in adult metabolic medicine Annalisa Sechi, et al https://doi.org/10.1002/jimd.12511

Dr Kimberly Goodspeed discusses a diverse group of patients with the rare lysosomal storage disorder, aspartylglucosaminuria, a condition most commonly seen amongst Finnish patients.

A cross-sectional natural history study of aspartylglucosaminuria Kimberly Goodspeed, et al https://doi.org/10.1002/jmd2.12294

Dr Thomas Cassini and Dr Carolina Montano from the NIH's Undiagnosed Diseases Program explain how they work to end the diagnostic journey for patients with undiagnosed conditions.

Diagnosis and discovery: Insights from the NIH Undiagnosed Diseases Program Carolina Montano, et al https://doi.org/10.1002/jimd.12506

The podcast welcomes Professor Maria Estela Rubio-Gozalbo and welcomes back Professor Judy Fridovich-Keil to talk mRNA therapy, gene therapy and disease models in classic galactosemia.

Novel mRNA therapy restores GALT protein and enzyme activity in a zebrafish model of classic galactosemia Britt Delnoy, et al https://doi.org/10.1002/jimd.12512

Neonatal GALT gene replacement offers metabolic and phenotypic correction through early adulthood in a rat model of classic galactosemia Jennifer M. I. Daenzer, et al https://doi.org/10.1002/jimd.12471

In this episode, Dr Gepke Visser, Dr Sacha Ferdinandusse and (soon to be Dr) Marit Schwantje discuss the Netherlands' experience of disorders of MTP activity detected on newborn screening. They also shed light on late-presenting disease phenotypes related to thermo-sensitivity.

Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands Marit Schwantje, et al https://doi.org/10.1002/jimd.12502

Thermo-sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy Marit Schwantje, et al https://doi.org/10.1002/jimd.12503

Edwin Kirk from the the Australian Reproductive Genetic Carrier Screening Project, discusses the challenges of implementing screening both prior to and during pregnancy.

Edwin would like to acknowledge the many international experts who have helped with variant classification, particularly in relation to the PMM2 variant mentioned in the podcast, and in particular would like to thank Belén Pérez and her team for their generosity in performing the functional assays.

Reproductive genetic carrier screening and inborn errors of metabolism: The voice of the inborn errors of metabolism community needs to be heard Edwin P. Kirk, Martin B. Delatycki, Nigel Laing https://doi.org/10.1002/jimd.12505

Dr Pierre-Axel Monternier discusses his group's work looking at a modified form of the drug pioglitazone to treat X-linked adrenaleukodystrophy.

Therapeutic potential of deuterium-stabilized (R)-pioglitazone—PXL065—for X-linked adrenoleukodystrophy Pierre-Axel Monternier, et al https://doi.org/10.1002/jimd.12510

Professor Manuel Schiff joins podcast host James Nurse to discuss a recent study looking at the successful use of Betaine in the management of early-onset MTHFR deficiency.

Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency Mathilde Yverneau, et al (2022) https://doi.org/10.1002/jimd.12504

Interested listeners may also want to read: Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency Martina Huemer, et al (2016) https://doi.org/10.1007/s10545-016-9991-4

Dr Sema Kalkan Uçar returns to the shortcast to present a cohort of 15 patients with MNGIE disease, including 9 with the p.P131L (c.392 C > T), or “Mediterranean” variant.

Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy Sema Kalkan Uçar, et al https://doi.org/10.1002/jmd2.12315

Dr Xiping Cheng joins podcast host James Nurse to explain her group's work exploring how glutaminase 2 knockdown could provide an alternative approach to management in Urea Cycle Disorders.

Glutaminase 2 knockdown reduces hyperammonemia and associated lethality of urea cycle disorder mouse model Xia Mao, et al https://doi.org/10.1002/jimd.12474

A team effort as Demi Beneru, Michel Tchan and Kate Billmore explain how they successfully supported a mother with GSD IIIa during her pregnancy.

Glycogen storage disease type IIIa in pregnant women: A guide to management Demi Beneru, Michel C. Tchan, Kate Billmore, Roshini Nayyar https://doi.org/10.1002/jmd2.12282

Robin Lachmann and Marc Patterson return to the podcast and are joined by their collaborator Dr Sandra Sirrs, to talk about their recent Editorial on drug development in rare disease.

Lost in translation—Challenges in drug development for inherited metabolic diseases Robin H. Lachmann, Marc C. Patterson, and Sandra Sirrs https://doi.org/10.1002/jimd.12501

Elaine Zaunseder and Dr Ulrike Mütze join the podcast to discuss the role of machine learning in newborn screening and why this is something clinicians need to know about.

Opportunities and challenges in machine learning-based newborn screening—A systematic literature review Elaine Zaunseder, et al https://doi.org/10.1002/jmd2.12285

The second half of our Barth Syndrome special issue tie in podcast features guest presenter Erik Lontok of the Barth Syndrome Foundation. The podcast looks at the work of Fred Vaz, Bill Pu, Jan Dudek, Christophe Maack and Adam Chicco, all of whom are working to advance our knowledge of Barth Syndrome.

Skip to specific papers at the timing below: Dr Fred Vaz, from 2 minutes Dr Bill Pu, from 14 minutes Dr Christophe Macao and Dr Jan Dudek, from 21:45 Dr Adam Chicco, from 31 minutes, 50 seconds.

Featured papers: An improved functional assay in blood spot to diagnose Barth syndrome using the monolysocardiolipin/cardiolipin ratio Frédéric M. Vaz, et al https://doi.org/10.1002/jimd.12425

Experimental models of Barth syndrome William T. Pu https://doi.org/10.1002/jimd.12423

Mechano-energetic aspects of Barth syndrome Jan Dudek & Christoph Maack https://doi.org/10.1002/jimd.12427

Long-chain fatty acid oxidation and respiratory complex I deficiencies distinguish Barth Syndrome from idiopathic pediatric cardiomyopathy Kathryn C. Chatfield, et al https://doi.org/10.1002/jimd.12459

In the first of two podcast intended to complement the January 2022 special issue, Dr Hilary Vernon joins the podcast to discuss the clinical presentation and natural history of Barth Syndrome and explore current and future treatments.

Clinical presentation and natural history of Barth Syndrome: An overview Carolyn Taylor, et al https://doi.org/10.1002/jimd.12422

Current and future treatment approaches for Barth syndrome Reid Thompson, et al https://doi.org/10.1002/jimd.12453

In honour of CDG Awareness Day, Dr Hudson Freeze and Dr Jaak Jaeken revisit a discussion from the Scientific CDG Symposium 2021, considering what makes a Congenital Disorder of Glycosylation.

CDG or not CDG Hudson H. Freeze, Jaak Jaeken and Gert Matthijs https://doi.org/10.1002/jimd.12498

Dr Cindy Towns presents seven cases of HCP from a single family with a novel mutation who have exhibited an unusually high penetrance and high rates of severe, recurrent attacks.

High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria Cindy Towns, et al https://doi.org/10.1002/jmd2.12281

Inherited Metabolic Diseases may have both a direct and indirect on dentition resulting on a number of challenges for parents, carers, clinicians and dentists when it comes to managing this. Dr Lorna Hirst and Dr Anupam Chakrapani join the podcast to explain what some of these issues are and why dentists should not be intimidated by IMD patients.

Inborn errors of metabolism and their impact in paediatric dentistry Lorna Hirst, Anupam Chakrapani, Suhaym Mubeen https://doi.org/10.1002/jimd.12493

Dr David Olsson discusses the Swedish experience following the introduction of newborn screening for VLCAD deficiency.

Very long-chain acyl-CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics David Olsson, et al https://doi.org/10.1002/jmd2.12268

Ashley Hertzog discusses the identification of an unexpected promoter variant as a cause of late-onset OTC deficiency.

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency Ashley Hertzog, et al https://doi.org/10.1002/jmd2.12289

Dr Rebecca Levy of the Lucile Packard Children's Hospital in Stanford, joins the podcast to discuss her recent work looking at epilepsy in NGLY1 deficiency.

Delineating the epilepsy phenotype of NGLY1 deficiency Rebecca J. Levy, et al https://doi.org/10.1002/jimd.12494

Dr Ronen Spiegel and Dr Bernd Schwahn join the podcast to discuss their natural history study in Molybdenum cofactor deficiency and the promise of treatment with cPMP for individuals with MoCD-A.

Molybdenum cofactor deficiency: A natural history Ronen Spiegel, et al https://doi.org/10.1002/jimd.12488

Dr Maria Fuller explains the clinical utility of the biomarker Chondrotin sulfate disaccharide in the diagnosis of MPSIVA.

Chondroitin sulfate disaccharide is a specific and sensitive biomarker for mucopolysaccharidosis type IVA Sharon J. Chin, et al https://doi.org/10.1002/jmd2.12132

Dr Kristin Ørstavik explains her team's observations of three patients with a novel mutation in the HADHB gene leading to a mild form of FTP deficiency.

Novel mutations in the HADHB gene causing a mild phenotype of mitochondrial trifunctional protein (MTP) deficiency Kristin Ørstavik, et al https://doi.org/10.1002/jmd2.12276

Professor Ranganath returns to the podcast and is joined by Dr Nick Sireau to discuss the SONIA 2 study, getting the Nitisinone dose right and how we should manage alkaptonuria in children.

Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling Lakshminarayan R. Ranganath, et al https://doi.org/10.1002/jmd2.12261

Effects of a protein-restricted diet on body weight and serum tyrosine concentrations in patients with alkaptonuria Birgitta Olsson, et al https://doi.org/10.1002/jmd2.12255

Professor Judy Fridovich-Keil discusses her work looking at acute and developmental outcomes in infants and young children with Duarte galactosemia.

Acute and early developmental outcomes of children with Duarte galactosemia Judith L. Fridovich-Keil, et al https://doi.org/10.1002/jmd2.12267

Dr George Diaz and Dr Spyros Batzios join the podcast to discuss a slight more unusual UCD, Arginase deficiency. They discuss the clinical features of the condition, the current management and a promising new therapy.

Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency Nandaki Keshavan, et al https://doi.org/10.1002/jmd2.12266

Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency George A. Diaz, et al https://doi.org/10.1002/jimd.12343

Dr Sema Kalkan Uçar discusses her observations around two siblings with galactose mutarotase deficiency. Available open access at the link below.

Two siblings with galactose mutarotase deficiency: Clinical differences Havva Yazici, et al https://doi.org/10.1002/jmd2.12263

Dr Megan Brophy and Dr Bob Bell join the podcast to talk about their recent work looking at AAV gene therapy in fibroblasts from patients with classic galactosemia. We discuss new insights into disease physiology and consider the challenges of scaling gene therapy towards in vivo model.

AAV-mediated expression of galactose-1-phosphate uridyltransferase corrects defects of galactose metabolism in classic galactosemia patient fibroblasts Megan L. Brophy, et al https://doi.org/10.1002/jimd.12468

Vicente Rubio, Belén Pérez, Santiago Ramón-Maiques join the podcast to discuss their recent work analysing the crystal structure of PMM2 and the insights this provides towards developing new treatments.

Insight on molecular pathogenesis and pharmacochaperoning potential in phosphomannomutase 2 deficiency, provided by novel human phosphomannomutase 2 structures Alvaro Briso-Montiano, et al https://doi.org/10.1002/jimd.12461

Dr Ashish Gupta and Dr Rene Pierpont of the University of Minnesota discuss their work looking at neurocognitive outcomes after transplant in childhood cerebral adrenoleukodystrophy.

Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy Ashish O. Gupta, et al https://doi.org/10.1002/jimd.12435

The first podcast of 2022 discusses two papers with negative outcomes and explores the importance of sharing such results for patients and families and clinicians working with rare disease. Dr Nicoline Løkken discusses her work with resveratrol in mitochondrial myopathies (from 5m 18s) and Dr Arunabha Ghosh and Professor Brian Bigger talk about the use of genistein in Sanfilippo syndrome (from 10m 38s).

No effect of resveratrol in patients with mitochondrial myopathy: A cross-over randomized controlled trial Nicoline Løkken, et al https://doi.org/10.1002/jimd.12393

High dose genistein in Sanfilippo syndrome: A randomised controlled trial Arunabha Ghosh, et al https://doi.org/10.1002/jimd.12407

Dr Gabriele Ramoser, Dr Federica Caferri, Dr Sabine Scholl-Bürgi and Dr Daniela Karall joined the podcast to discuss their recent work looking at the Austrian "Registry for Inherited Metabolic Disorders". We spoke about the importance of patient registries, variable prevalence rates and the difficulties around where to care for adults with IMD.

100 years of inherited metabolic disorders in Austria—A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021 Gabriele Ramoser, et al https://doi.org/10.1002/jimd.12442

In March 2021 our special issue look at all aspects of Mitochondrial Disease. In this special episode Professor Shamima Rahman guest hosts as we welcome David Dimmock, Mike Lawlor, Guilhian Leipnitz and Marc Patterson to discuss their papers from that issue, looking at novel therapies in mitochondrial disease.

For those skipping: DGUOK (from 3min 30sec), SO deficiency (from 19min) and Friedreich's Ataxia (29min 10sec).

The nucleotide prodrug CERC-913 improves mtDNA content in primary hepatocytes from DGUOK-deficient rats Vanden Avond, et al https://doi.org/10.1002/jimd.12354

The mitochondrial-targeted reactive species scavenger JP4-039 prevents sulfite-induced alterations in antioxidant defenses, energy transfer, and cell death signaling in striatum of rats Glänzel, et al https://doi.org/10.1002/jimd.12310

Safety and efficacy of (+)-epicatechin in subjects with Friedreich's ataxia: A phase II, open-label, prospective study Qureshi, et al https://doi.org/10.1002/jimd.12285

Associate Professor Sabine Fuchs and PhD Candidate Vivian Lehmann join the podcast to explain cholangiocyte organoids and the role they play in understanding rare disease and testing new treatments.

The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism Vivian Lehmann, et al https://doi.org/10.1002/jimd.12450

The podcast is joined by the wonderful Dr Sander Houten and Dr Pablo Ranea-Robles who explain their recent working looking at the ATP binding cassette ABCD3 in dicarboxylic fatty acid metabolism.

The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis Pablo Ranea-Robles et al https://doi.org/10.1002/jimd.12440

Dr Sandra Kingma from the Centre for Rare Diseases in Antwerp joins the podcast to discuss all things Mucopolysaccharidosis type I. Her recent paper asks 'where are we now?' and I asked her about where we are going next?

MPS I: Early diagnosis, bone disease and treatment, where are we now? Sandra D. K. Kingma, An I. Jonckheere, First published: 03 September 2021 https://doi.org/10.1002/jimd.12431

Dr Marc Patterson and Dr Eugen Mengel explain the challenges of treating Niemann Pick Type C. Recent studies have shown the efficacy of Miglustat and Arimoclomal but they may end up forming just part of the puzzle being built to manage this condition.

Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment Eugen Mengel, et al https://doi.org/10.1002/jimd.12428

Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: A large retrospective observational study Marc C. Patterson, et al https://doi.org/10.1002/jimd.12245

Dr Chiara Pizzamiglio of the Department of Neuromuscular Diseases at Queen Square discusses her recent publication looking at a huge cohort of 197 patients with McArdle disease. Dr Pizzamiglio hi-lights the diagnostic challenges in this GSD and shows new insights into the spectrum of extra-muscular manifestations seen in the condition.

Phenotype and genotype of 197 British patients with McArdle disease: An observational single-centre study Chiara Pizzamiglio et al https://doi.org/10.1002/jimd.12438

Professor Warren Kruger of the Fox Chase Cancer Centre in Philadelphia joins the podcast to talk about homocystinuria, successful trials in gene therapy, why it costs so much to make viruses and what inspires him.

Long-term functional correction of cystathionine β-synthase deficiency in mice by adeno-associated viral gene therapy Hyung-Ok Lee et al https://doi.org/10.1002/jimd.12437

Interested listeners may also wish to look at: Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency Andrew A. M. Morris, et al https://doi.org/10.1007/s10545-016-9979-0

Dr Elaine Murphy and Dr Robin Lachmann of the Charles Dent Metabolic Unit, look after over 400 adults with PKU. They join the podcast to discuss their recent work on long-term outcomes in early-treated Phenylketonuria and to hi-light some of their more interesting findings.

Long-term cognitive and psychosocial outcomes in adults with phenylketonuria Lynne Aitkenhead et al https://doi.org/10.1002/jimd.12413

In the latest podcast we've returning guest Professor Thorsten Marquardt and his colleague Dr Jörn Oliver Sass talking about their work with 3-Hydroxyisobutyrate dehydrogenase deficiency. Thorsten reports their success in using a low valine diet for an affected patient and Oliver discusses the challenge of differentiating disorder metabolism from disease.

3-Hydroxyisobutyrate dehydrogenase (HIBADH) deficiency—A novel disorder of valine metabolism Melanie Meyer et al https://doi.org/10.1002/jimd.12410

Melissa Broeks speaks with the podcast about her recent paper reviewing disorders of the malate aspartate shuttle, an essential pathway supporting respiratory chain activity. Melissa provides a wonderful overview of the background and clinical significance of the MAS, all of which can be explored further in her #openaccess paper.

Inborn disorders of the malate aspartate shuttle Melissa H. Broeks, et al https://doi.org/10.1002/jimd.12402

The 'Junge Stoffwechselmedizin' or Young Metabolic Society is an initiative in Germany intended to support early career doctors, dieticians, scientists and nurses interested in the IMD field. Young metabolists, Dr Heiko Brennenstuhl and Dr Vanessa Kock, explain just what it's all about.

They warmly welcome anyone who shares their vision of shaping the future of metabolic medicine in Europe (and beyond) to get in touch via info@junge-stoffwechselmedizin.de. The “Young Metabolic Society”: An interest group for young professionals in the field of metabolic medicine https://doi.org/10.1002/jimd.12409

Professors Jun Kido, Johannes Häberle and Fanny Mochel discuss their recent work on Urea Cycle Disorders to hi-light the significance of this group of diseases. Jun and Johannes collaborated on a large natural history study in Japan of over 270 patients and Fanny recently reported on a large cohort of adults presenting with disease from 16-86 years of age. All three relate these findings to the first revision of the Guidelines for Management published in 2019.

Long-term outcome of urea cycle disorders: Report from a nationwide study in Japan Jun Kido, et al https://doi.org/10.1002/jimd.12384

Adult-onset diagnosis of urea cycle disorders: Results of a French cohort of 71 patients Ségolène Toquet, et al https://doi.org/10.1002/jimd.12403

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision Johannes Häberle, et al https://doi.org/10.1002/jimd.12100

Professor Robin Lachmann of the Charles Dent Metabolic Unit discusses the science behind Enzyme Replacement Therapy and Gene Therapy and explains why these do, and sometimes do not, work in Lysosomal Storage Disorders. Professor Lachmann also discusses the progress towards establishing adult metabolic services in the UK and elsewhere.

Treating lysosomal storage disorders: What have we learnt? Robin H. Lachmann https://doi.org/10.1002/jimd.12131

Education and training in adult metabolic medicine: Results of an international survey Annalisa Sechi, et al https://doi.org/10.1002/jmd2.12044

Johannes Zschocke, Shamima Rahman, and Carlos Ferreira join hosts James Nurse and Eva Moreva to discuss their recent paper on the ICIMD, a new classification system that eloquently organises all things metabolic. They explain what's included, why it is necessary and just how simple it all is. Interested listeners should also read: Quo vadis: the re-definition of “inborn metabolic diseases” (https://doi.org/10.1007/s10545-015-9893-x)

An International Classification of Inherited Metabolic Disorders Carlos R. Ferreira et al.

https://onlinelibrary.wiley.com/doi/10.1002/jimd.12348

Dr Terry Derks is joined by co-author, collaborator and IMD parent, Sebastiaan te Boekhorst to discuss the emergencyprotocol.net website, an initiative to empower families and standardise care for children with FAOD and GSDs. Alongside Terry and Sebastiaan are Enrique Landelino “Lande” Contreras and Marta D’Agosto, parents of Nina, a little glycogen storage disease warrior, sharing their thoughts on what this work means to them.

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: A retrospective, single-center study and the generation of www.emergencyprotocol.net Alessandro Rossi et al.

https://doi.org/10.1002/jimd.12386

View from inside: Nina, Glycogen storage disease warrior Written by Nina's Parents: Enrique Landelino “Lande” Contreras and Marta D'Agosto

https://doi.org/10.1002/jimd.12246

The Congenital Disorders of Glycosylation are a rapidly growing group of IMDs but can present a number of diagnostic challenges. In this podcast, Dr Julien Park, Dr Robert Mealer, and Professor Thorsten Marquardt discuss an additional technique for assessing glycosylation and its role in the diagnosis and management of SLCC39A-CDG.

N‐glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency Julien H. Park et al.

https://doi.org/10.1002/jimd.12306

Professor Judith Fridovich-Keil has been researching galactosemia for over 20 years and it was a privilege to welcome her to the JIMD podcast. The Professor and one of her former lab students and now medical student, Jessica MacWilliams, discuss the promise of new treatments, what drives their interest in galactosemia and a new method for formally assessing fine motor control in these patients.

A pilot study of neonatal GALT gene replacement using AAV9 dramatically lowers galactose metabolites in blood, liver, and brain and minimizes cataracts in GALT‐null rat pups Shauna A. Rasmussen et al. https://doi.org/10.1002/jimd.12311

Hand fine motor control in classic galactosemia Jessica MacWilliams et al. https://doi.org/10.1002/jimd.12376

Dr Patrick Forny and Dr Matthias Baumgartner join our social media editor to discuss their work on the first revision to the guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia. This follow-up to a very popular resource takes a new approach to reviewing evidence and discusses the latest advances in the field.

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision Patrick Forny et al.

https://doi.org/10.1002/jimd.12370

Dr Monique Williams joins us on the podcast to discuss the European experience of transplantation in Inherited Metabolic Disease. There’s currently no central record of procedures or outcomes and Dr Williams and her team are keen to standardise management around transplant and ensure that there is a robust evidence base.

Liver and/or kidney transplantation in amino and organic acid‐related inborn errors of metabolism: An overview on European data Femke Molema et al.

https://doi.org/10.1002/jimd.12318

Authors Dr Kim Hemsley and Nazzmer Nazri, from the Childhood Dementia Research Group, are joined by their colleague Dr Nick Smith to discuss their recent paper, as well as the wider implications of heterozygosity for Lysosomal Storage Disorders (LSDs) and whether these are associated with early-onset neurodegenerative disease. 50000 children a year are born with conditions associated with childhood dementia and as many as 1 in 40 people carry mutations associated with LSDs so the implications of their work are potentially very wide-ranging.

Is SGSH heterozygosity a risk factor for early‐onset neurodegenerative disease? Meghan L. Douglass et al. https://doi.org/10.1002/jimd.12359

It was a pleasure to be joined by the inimitable Professor Lakshminarayan Ranganath to discuss all things AKU. Ranga spoke about the outcomes of two recent papers looking at his centre’s experience using Nitisinone in these patients but also explains disease physiology, the history of drug discovery, new insights into the disease and upcoming research; 120 years of metabolic medicine in 25 minutes.

Characterizing the alkaptonuria joint and spine phenotype and assessing the effect of homogentisic acid lowering therapy in a large cohort of 87 patients Lakshminarayan R. Ranganath, Milad Khedr, Sobhan Vinjamuri & James A. Gallagher https://doi.org/10.1002/jimd.12363

Characterising the arthroplasty in spondyloarthropathy in a large cohort of eighty‐seven patients with alkaptonuria Lakshminarayan R. Ranganath, James A. Gallagher, John Davidson & Sobhan Vinjamuri https://doi.org/10.1002/jimd.12340

Dr Giuseppe Ronzitti and Dr Alan O’Brien discuss their recent paper of Glycogen Storage Disorder Type III. They discuss the clinical features of the condition, new insights around the age of onset of muscular symptoms and treatments in use today, as well as those being research for use in the years to come.

Narrative review of glycogen storage disorder type III with a focus on neuromuscular, cardiac and therapeutic aspects Édouard Berling et al. https://doi.org/10.1002/jimd.12355

Dr Uwe Kornak and Dr Björn Fischer-Zirnsak explain all things cutis lava to our social media editor, and explain how their recent work helps further define the clinical description of ATP6V1A disease.

Expanding the clinical and molecular spectrum of ATP6V1Arelated metabolic cutis laxa Guido Vogt MSc et al. https://doi.org/10.1002/jimd.12341

In the 16th podcast from the Journal of Inherited Metabolic Disease, Dr Stephan Kemp and Dr Eric Mallack join our social media editor to discuss their recent papers on X-linked adrenoleucodystrophy. Dr Kemp explains how a variety of model systems are used to aid disease understanding and help in the development of new therapies, whilst Dr Mallack shares new guidance around surveillance for the onset of cerebral ALD in childhood.

MRI surveillance of boys with X‐linked adrenoleukodystrophy identified by newborn screening: Meta‐analysis and consensus guidelines Eric J. Mallack et al. https://doi.org/10.1002/jimd.12356

Evolution of adrenoleukodystrophy model systems Roberto Montoro et al. https://doi.org/10.1002/jimd.12357

Peter Clayton, Emma Footitt and Curtis Coughlin join us to discuss the new consensus guidelines for PDE-ALDH7A1 disease. Professor Clayton explains the pathophysiology and history of the condition. Dr Footitt and Dr Clayton discuss the metabolic investigations of early onset seizures as well as the proposed management of pyridoxine-dependent epilepsy.

Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency Curtis R. Coughlin et al. https://doi.org/10.1002/jimd.12332

Professor Jerry Vockley joins our social media editor, James Nurse, to discuss a recent paper looking at the use of Triheptanoin (C7) in patients with long chain fatty acid oxidation disorders.

Listeners may also be interested in the emotive editorial: View from inside: Rare diseases in the times of COVID19 (https://doi.org/10.1002/jimd.12334)

Effects of triheptanoin (UX007) in patients with long‐chain fatty acid oxidation disorders: Results from an open‐label, long‐term extension study Jerry Vockley et al. https://doi.org/10.1002/jimd.12313

The journal recently published two articles on TANGO2 deficiency, describing a case series of 20 patients and exploring the uncertain pathophysiology of this condition. Dr Sebastian Montealgre, Dr Pascale de Lonlay, Dr Felix Distelmaier and Dr Michael Sacher joined our social media editor to explain what they observed and the implications of those findings.

Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect Claire‐Marine Bérat et al. https://doi.org/10.1002/jimd.12314

The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER‐to‐Golgi transport and at the mitochondria Miroslav P. Milev et al. https://doi.org/10.1002/jimd.12312

Dr Cecilia Marelli and Dr Fanny Mochel discuss their recent work, looking at the largest case series of adults with late-onset MTHFR deficiency described so far. They discuss the clinical phenotype and diagnostic approach to this treatable, neurodegenerative disorder.

Clinical and molecular characterization of adult patients Cecilia Marelli et al.

https://doi.org/10.1002/jimd.12323

This episode hi-lights JIMD Reports, the open access companion journal to the Journal of Inherited Metabolic Disease. We’ve chosen to hi-light 5 very different papers and are joined by 7 of the authors to discuss their work. Professor Eileen Treacy discusses Trimethylaminuria, Dr Khushbu Patel and Dr Bill Phipps explain alternative amino acid analysis techniques (at 00:07:30), Dr Joyanna Hansen looks at what the Simplified Diet means in the US (00:13:13), Dr Amy Kritzer explains why they skimmed breast milk for an infant with a long-chain fatty acid oxidation disorder (00:19:08) and Professor Simon Heales and Dr Stefan Krywawych look at the utility of ear wax for detecting IMD (00:24:37).

The genetic and biochemical basis of trimethylaminuria in an Irish cohort Samantha Doyle et al.

https://doi.org/10.1002/jmd2.12028

Quantitative amino acid analysis by liquid chromatography‐tandem mass spectrometry using low cost derivatization and an automated liquid handler William S. Phipps et al.

https://doi.org/10.1002/jmd2.12080

Simplified Diet for nutrition management of phenylketonuria: A survey of U.S. metabolic dietitians Joyanna Hansen et al.

https://doi.org/10.1002/jmd2.12106

Use of skimmed breast milk for an infant with a long‐chain fatty acid oxidation disorder: A novel therapeutic intervention Amy Kritzer et al.

https://doi.org/10.1002/jmd2.12152

Earwax: A potentially useful medium to identify inborn errors of metabolism? Stefan Krywawych et al.

https://doi.org/10.1002/jmd2.12102

Dr Lars Schlotawa, Dr Rebecca Ahrens‐Nicklas and Dr Laura Adang, as well as MSD parent and disease advocate Alan Finglas, discuss two recent studies on Multiple Sulfatase Deficiency. Alan shares his insights on disease advocacy and what work like this means to him and his family.

Natural history of multiple sulfatase deficiency: Retrospective phenotyping and functional variant analysis to characterize an ultra‐rare disease Laura A. Adang et al.

https://doi.org/10.1002/jimd.12298

A systematic review and meta‐analysis of published cases reveals the natural disease history in multiple sulfatase deficiency Lars Schlotawa et al.

https://doi.org/10.1002/jimd.12282

View from inside: When multiple sulfatase deficiency changes everything about how you live and becomes your life Alan Finglas

https://doi.org/10.1002/jimd.12305

Dr Michio Hirano and Dr Rita Rinaldi discuss their recent work that summarises a 2 day consensus conference to provide guidance on the diagnosis, prognosis and treatment of Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network Michio Hirano et al.

https://doi.org/10.1002/jimd.12300

Professor Eva Morava and Dr James Nurse host three of the authors of a recent study looking at the utility whole exome sequencing in newborn screening. Dr Jennifer Puck, Dr Renata Gallagher and Dr Aashish Adhikari explain why we screen, how we screen like we do and what they found when they looked at the utility of WES screening verses traditional MS/MS for 8 years of dried bloodspots in California.

Newborn screening: To WES or not to WES, that is the question Eva Morava, Matthias Baumgartner, Marc Patterson, Verena Peters, Shamima Rahman

https://doi.org/10.1002/jimd.12303

Dr Jong Rho of Rady Children’s Hospital discusses metabolic epilepsies amenable to the ketogenic diet. Dr Rho explains the effects of the diet on the body and why it is effective in certain forms of inherited metabolic disease.

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms Cezar Gavrilovici, Jong M. Rho

https://doi.org/10.1002/jimd.12283

Professor Shamima Rahman speaks with Social Media editor James Nurse about the challenges of conducting clinical trials in mitochondrial disease and developments in treatment. Professor Rahman explains that improvements in diagnostics have allowed a renewed focus on treatments.

Moving Towards Clinical Trials for Mitochondrial Diseases Robert D.S. Pitceathly, Nandaki Keshavan, Joyeeta Rahman, Shamima Rahman

https://doi.org/10.1002/jimd.12281

Professor Eva Morava of the Mayo Clinic takes us through the recently published consensus statement on the diagnosis and management of PGM1-CDG. Professor Morava provides a concise background to Congenital Disorders of Glycosylation and PGM1 disease specifically, and she explains how to recognise and diagnose this rare but treatable condition.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1‐CDG): diagnosis, follow‐up and management Altassan et al

https://doi.org/10.1002/jimd.12286

Interested listeners may also want to read the consensus statement for PMM2-CDG published at the start of this year (https://doi.org/10.1002/jimd.12024).

Professor Saudubray and Professor Garcià-Cazorla discuss their paper from 2019 which proposed a simplified classification of IMD. They discuss the challenges of placing over 1000 diagnoses in one of three categories and the value this provides to clinicians.

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians Jean‐Marie Saudubray et al

https://doi.org/10.1002/jimd.12086

Professor Peter Clayton of the Institute for Child Health speaks to the JIMD Podcast about recent findings suggesting that an inborn error in a proline transporter could increase susceptibility to severe CoVID19 disease.

Is susceptibility to severe COVID ‐19 disease an inborn error of metabolism? Peter Clayton

https://doi.org/10.1002/jimd.12280

Professor Bindoff and Professor Gorman, two luminaries of the world of mitochondrial medicine, speak with James Nurse about recent work in JIMD expanding knowledge on safe drug use in Primary Mitochondrial Disease. Professor Bindoff also explains a proposed classification for Polymerase Gamma disease including when to suspect this condition and how to investigate it.

Safety of drug use in patients with a primary mitochondrial disease: An international Delphi‐based consensus Maaike C. De Vries et al

https://doi.org/10.1002/jimd.12196

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases Omar Hikmat et al

https://doi.org/10.1002/jimd.12211

Dr Emma Vardy, a Consultant Geriatrician from Salford, UK, explains the findings of a recent JIMD review looking at the impact of phenylketonuria in adulthood. With those who have benefitted from early treatment now approaching their fifth and sixth decades, PKU cannot just be seen as a disease of childhood and more work is needed to look into the long term impact of the condition.

Phenylketonuria, co‐morbidity, and ageing: A review Emma R.L.C. Vardy, Anita MacDonald, Suzanne Ford, Denise L. Hofman

https://doi.org/10.1002/jimd.12186