JIMD Podcasts

A young girl develops progressive neurological symptoms and a biomarker profile pointing strongly towards a particular metabolic disorder. There's just one problem: the genetic testing is negative. In this Metabolic Mystery, Dr Ayca Burcu Kahraman follows the clues beyond conventional DNA testing to finally crack the case. Can you solve it before she does? Read the paper: https://doi.org/10.1055/a-2903-9323

A 7-year-old boy presents following a suspected seizure, with a history of progressive ataxia and tremor. An MRI offers an important clue but a seemingly reassuring blood result complicates the picture. In this Metabolic Mystery, Dr Steven Lang follows the clues to uncover a treatable metabolic diagnosis. Can you solve the case before he does? Read the paper: https://doi.org/10.1542/pir.2025-007029

Cytopenias and infections are familiar complications of branched-chain organic acidemias, but are they simply consequences of metabolic decompensation? Abdul Shakerdi and Jerry Vockley join the JIMD Podcast to explore evidence that persistent immune dysfunction and inflammation may be fundamental parts of the disease phenotype, with implications for clinical care, research and emerging therapies. Immune Dysregulation in Branched Chain Organic Acidemias Abdul L. Shakerdi, et al https://doi.org/10.1002/jimd.70203

In this JIMD Reports Shortcast, Dr Eamon McCarron presents a challenging pregnancy in a woman with lysinuric protein intolerance complicated by immune dysregulation and severe thrombocytopenia. Hear how multidisciplinary management supported a favourable outcome for both mother and baby. Pregnancy in Lysinuric Protein Intolerance Complicated by Immune Dysregulation and Severe Thrombocytopenia Eamon P. McCarron, et al https://doi.org/10.1002/jmd2.70109

Could some mitochondrial disorders also be treatable interferonopathies? In a new JIMD Reports Shortcast, Dan Brooks and Fernando Scaglia look at a fascinating case of PNPT1-related mitochondrial disease in which mitochondrial dysfunction was accompanied by activation of the type I interferon pathway. Treatment with the JAK inhibitor tofacitinib normalised the interferon signature and was associated with improvements in biochemical and clinical measures. As a single case it is necessarily preliminary, but it provides an intriguing example of how understanding the crosstalk between mitochondria and the immune system might open up new therapeutic approaches. JAK Inhibition in PNPT1-Related Mitochondrial Interferonopathy: A Case Report and Review of Mitochondrial–Immune Crosstalk Dan Ross Brooks, et al https://doi.org/10.1002/jmd2.70096

In the fifth, and thankfully final, update from Helsinki, James and Silvia return to provide their inimitable take on the sessions from Thursday with a look ahead to Friday's sessions. They find themselves looking well beyond the last day, as James speaks with Dr Ina Knerr about preparations for the SSIEM 2027 meeting in Dublin. James gets yet another geography lesson and we hear from a bumper helping of conference attendees finally keen to discuss their posters. So long Helsinki, it's been wonderful.

James and Silvia return for the 4th episode of their increasingly confusing daily podcast from the SSIEM 2026 annual meeting in Helsinki. The flood gates have finally opened and we hear from multiple guest about their posters and presentations, and Dr Nazi Tabatadze caught up with James to give him a quick geography lesson and discuss IMD care in Georgia. You've just one more day to be part of the podcast so say hello or forever wonder about the life of fame and fortune that you let slip away.

Silvia and James reflect on the first full day of the SSIEM 2026 meeting and look ahead to day 2. They check in with Rodrigo to find out why he can't be Helsinki and welcome a number of contributors who encourage you to come and see their posters. Remember, there are now just two days left to be a part of the podcast no-one asked for... find them, before they find you.

Hosts Silvia Radenkovic and James Nurse return to introduce the first 'proper' day of the SSIEM 2026 meeting. In addition to highlighting some of the unsung highlights of Day 1 (lab proficiency testing anyone), Silvia makes her case as a mentor and James speaks with Dr Narmin Aslanzade and Dr Leman Alirzayeva about IMD services in Azerbaijan and the posters they're bringing to SSIEM 2026. As always, Silvia and James would love to hear from you so if you're at the meeting and want to shout about your poster, please get in touch.

The "podcast no one asked for" is back as hosts Silvia Radenkovic and James Nurse preview the 2026 SSIEM Annual Meeting, and they are joined by meeting chair Risto Lapatto to discuss what goes in to arranging an international IMD conference, the sessions he doesn't want to miss and why you have to try a sauna. We want to hear from you across the week so if you've got a poster in Helsinki please get in touch and we will find you!!

Raphaela Muri and Roman Trepp join the JIMD Podcast to explore what happens to the adult brain in phenylketonuria. We discuss the effects of phenylalanine exposure on brain structure, what MRI studies reveal about potentially reversible changes, how these findings relate to cognition, and whether the latest evidence really suggests altered brain ageing in early-treated PKU. Papers discussed and related work Brain Age in Adult Patients With Early-Treated Phenylketonuria Winiger et al. https://doi.org/10.1002/jimd.70158 Neural Correlates of Working Memory and Its Association With Metabolic Parameters in Early-Treated Adults With Phenylketonuria Abgottspon et al. https://doi.org/10.1016/j.nicl.2022.102974 Cortical Thickness and Its Relationship to Cognitive Performance and Metabolic Control in Adults With Phenylketonuria Muri et al. https://doi.org/10.1002/jimd.12561 Do Early-Treated Adults With Phenylketonuria Sense High Phenylalanine Levels? Hauri et al. https://doi.org/10.1002/jmd2.12446 Cerebral Blood Flow and White Matter Alterations in Adults With Phenylketonuria Steiner et al. https://doi.org/10.1016/j.nicl.2023.103550 Reversible White Matter Changes Following a 4-Week High Phenylalanine Exposure in Adults With Phenylketonuria Muri et al. https://doi.org/10.1002/jimd.12823 Transient Brain Structure Changes After High Phenylalanine Exposure in Adults With Phenylketonuria Muri et al. https://doi.org/10.1093/brain/awae139 Cognition After a 4-Week High Phenylalanine Intake in Adults With Phenylketonuria – A Randomized Controlled Trial Trepp et al. https://doi.org/10.1016/j.ajcnut.2023.11.007 Are Functional Brain Networks Sensitive to High Phenylalanine in Adults With Phenylketonuria? Vallesi et al. https://doi.org/10.1002/jmd2.70108

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 Metabolism Júlio César Rocha, Anne Daly, Anita MacDonald https://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 Interventions Sarah J. Firman, et al https://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 al https://doi.org/10.1002/jimd.70094 Screening for Life: Perspectives From Adult Metabolic Specialists on Newborn Screening for Inherited Metabolic Diseases. M Langeveld, et al. https://doi.org/10.1002/jimd.70057 Exclusion-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 Genetics J Gold et al https://www.cell.com/ajhg/fulltext/S0002-9297(25)00238-1 Long-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 C Benjamín Szenfeld, et al https://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 Disease Arthavan Selvanathan, et al https://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 Study Engin Köse, et al https://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 IVB Mark Wijnen, Evert F. S. van Velsen, J. Gert-Jan Milhous, Esmee Oussoren, Bram C. J. van der Eerden, Margreet A. E. M. Wagenmakers First 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 Clinicians Arthavan Selvanathan, et al https://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 research A 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 Series U. Diaz-Moreno, et al https://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 Adrenoleukodystrophy Troy C. Lund, et al https://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 Gangliosidosis Kyle Landskroner, Kshitiz Singh, Melissa Mitchell, Jagdeep S. Walia https://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

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 Deficiency Sophie 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 Enzyme Anne Korwitz-Reichelt, et al https://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 Features Rory J. Tinker, et al https://doi.org/10.1002/jmd2.70068

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

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 Diseases Sonam 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 Deficiency Aaron B. Bowen, et al https://doi.org/10.1002/jmd2.70072

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

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

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, 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.