JIMD Podcasts

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://d...

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 D...

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 Prospe...

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....

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...

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 homocy...

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...

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...

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...

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: http...

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.org Consensus Guideline for the Diagnosis and Treatment...

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 Korw...

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 F...

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...

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 Superimp...

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 Fibrobla...

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 meta...

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 Met...

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 Repo...

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 sometime...

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 t...

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 D...