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 👉 https://www.proms-ntd.org

Consensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) Deficiency

Mariya Sigatullina Bondarenko, et al

https://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 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

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

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