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