JIMD Podcasts

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 Deficiency Aaron B. Bowen, et al https://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 remodeling 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 Fibroblasts Eduardo Vieira Neto, et al https://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 Diagnosis Molly M. Crenshaw, et al First 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.

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 Disease Sophie Manoy, et al https://doi.org/10.1002/jmd2.70051

Supplement prescribing in primary mitochondrial disease is almost universal, yet highly individualised, stepwise, and non-uniform across regions and phenotypes, with real potential for tissue and pill-burden harm. This podcast features Dr Julia Neugebauer and Professor Shamima Rahman exploring findings of a recent MetabERN survey looking at what informs when clinicians start, monitor, and sometimes stop enzymes and co-factors, and how global registry and natural-history data may guide the field forward. Current global vitamin and cofactor prescribing practices for primary mitochondrial diseases: Results of a European reference network survey Julia Neugebauer, et al https://doi.org/10.1002/jimd.12805 And the editorial discussed: Should the "mitochondrial cocktail" be a default option? An opinion Peter W Stacpoole, Stephen D Cederbaum https://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 Dysfunction Herodes Guzman, et al https://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 Care Anja Lee, et al https://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 Signs Merve Yoldaş Çelik, et al https://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 2 Sherry Fang, et al https://doi.org/10.1002/jimd.70031 Removal of Toxic Metabolites—Chelation: Manganese Disorders Hendrik Vogt, et al https://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 Report Jeremy Clark, et al https://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 Flashback Jean-Marie Saudubray, Manuel Schiff https://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 Diseases Terry G. J. Derks, et al https://doi.org/10.1002/jimd.70040 and A deep learning approach for blood glucose monitoring and hypoglycemia prediction in glycogen storage disease Ji Seung Ryu, et al https://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 Alignment Krista Casazza, et al https://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 Management A. Terrell, et al https://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 al https://doi.org/10.1002/jimd.70069 Editorial Comment to Regulatory News Carla E. M. Hollak, Natalja Bouwhuis https://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 al Mitochondrial 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 al FGF21 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 al Protein 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 al An 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 al Hypoxia 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 al Metabolomics 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.

Here’s a polished podcast blurb suitable for LinkedIn, BlueSky, or Apple Podcasts listings — written in the JIMD Podcast tone and style: ⸻ It’s one of the most talked-about breakthroughs of 2025, a first-in-human demonstration of in vivo gene editing to treat an inherited metabolic disease. In this episode, Kiran Musunuru and Rebecca Ahrens-Nicklas are joined by Julien Baruteau to unpack what this means for the field. They explore the science behind gene editing, the importance of ethical design, and the emotional weight of stopping therapy once enzyme function is restored. The conversation bridges the NEJM landmark paper (Musunuru et al., 2025) and the accompanying JIMD editorial (Rahman & 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 Disease Shamima Rahman, Julien Baruteau https://doi.org/10.1002/jimd.70056 Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease Kiran Musunuru, et al https://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