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://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