Treatment is available for most intoxication-type disorders, but would you know what to do in an emergency. In this podcast, Dr Dexter Tarr discusses the acute management when these conditions cause encephalopathy, seizures, stroke-like episodes, thromboses, liver failure, cardiac failure, arrhythmias and rhabdomyolysis.

Emergency Management of Intoxication-Type Inherited Metabolic Disorders

J. Dexter Tarr, Andrew A. M. Morris

https://doi.org/10.1002/jimd.70007

Michel Tchan and Mirjam Langeveld join the podcast to look at changes to adult IMD services over the last decade and consider the challenge to develop services to meet the needs of growing patient numbers over the next 10 years.

The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: 10 Years Later, Another Report From the SSIEM Adult Metabolic Physicians Group

Michel Tchan, et al

https://doi.org/10.1002/jimd.70005

Dr Sabine Fuchs, Professor of Metabolic diseases and innovative therapies at the UMC Utrecht, and Dr Sean Froese, a Principal Investigator in the Metabolism Division at University Children’s Hospital Zürich, join Rodrigo and Silvia to discuss new insights and some of their favourite papers on Methylmalonic Aciduria.

Authors opinions are their own and do not represent their institutions.

Papers discussed include:

Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency

Forny et al

Aberrant methylmalonylation underlies methylmalonic acidemia and is attenuated by an engineered sirtuin.

Head et al

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

Manoli et al

Prime editing for functional repair in patient-derived disease models

Schene et al

Mutation-specific reporter for optimization and enrichment of prime editing

Schene et al

Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.

Manoli et al

Fibroblast growth factor 21 as a biomarker for long-term complications in organic acidemias.

Molema et al

Lucas Agnoletto and Dr Rebecca Halligan report work looking at sleep quality in children with hepatic GSDs, considering whether sleep is impacted by poor glycemic control or our efforts to improve this through overnight feeding.

Sleep quality in children with hepatic glycogen storage diseases, a prospective observational pilot study

Lucas Agnoletto, et al

https://doi.org/10.1002/jmd2.12462

Dr Carole Linster and Dr Nicole van Bergen explain why metabolism isn't perfect and how disorders of enzyme repair present their own challenges. In an episode that explores Niacin and longevity, we also hear why NAXD deficiency is an important differential in acute cardiomyopathy and provides an aetiology that could be highly amenable to treatment.

Clinical and biochemical distinctions for a metabolite repair disorder caused by NAXD or NAXE deficiency

Nicole J. Van Bergen, et al

https://doi.org/10.1002/jimd.12541

NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses

Nicole J Van Bergen, et al

https://doi.org/10.1093/brain/awy310

Severe NAD(P)HX Dehydratase (NAXD) Neurometabolic Syndrome May Present in Adulthood after Mild Head Trauma

Nicole J Van Bergen, et al

https://doi.org/10.3390/ijms24043582

Asthik Biswas, Spyros Batzios, and Kshitij Mankad expand on their recent letter to the editor to explain why ushering in the new era of gene therapy treatments requires not just clinical but also imaging readiness.

Imaging readiness in the gene therapy era-exploring standardized protocols for response assessment

Asthik Biswas, et al

https://doi.org/10.1002/jimd.12828

Dr Matthew Wilson, Postdoctoral Fellow at the Centre for Human Genetics, KU Leuven, joins hosts Silvia Radenkovic and Rodrigo Starosta to discuss a scintillating selection of CDG papers in our first ever research round-up.

Authors opinions are their own and do not represent their institutions.

The papers discussed include:

A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis.

Wilson et al

Clinical and biochemical footprints of congenital disorders of glycosylation: Proposed nosology.

Ng et al

Rft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane.

Chen et al

Molecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG.

Hirata et al

Genome and RNA sequencing were essential to reveal cryptic intronic variants associated to defective ATP6AP1 mRNA processing.

Morales-Romero et al

N-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts.

Garapati et al

In vitro treatment with liposome-encapsulated Mannose-1-phosphate restores N-glycosylation in PMM2-CDG patient-derived fibroblasts.

Shirakura et al

Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation.

Budhraja et al

D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG).

Starosta et al

Glycoproteomics in Cerebrospinal Fluid Reveals Brain-Specific Glycosylation Changes.

Baerenfaenger et al

Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models.

Radenkovic et al

Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort

Lam et al

It's an Arg1 extravaganza as Reena Sharma, Sara Olofsson, Karolina Stepien and Alison Woodall discuss three separate papers looking at the Salford Royal experience of a cohort of adults with Arginase 1 deficiency and the wider health and societal cost of the condition.

Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centre

Reena Sharma et al

https://doi.org/10.1002/jmd2.12450

Disease burden among patients with Arginase 1 deficiency and their caregivers: A multinational, cross-sectional survey

Sara Olofsson et al

https://doi.org/10.1002/jmd2.12456

Societal costs and quality of life associated with arginase 1 deficiency in a European setting – a multinational, cross-sectional survey

Sara Olofsson et al

https://doi.org/10.1080/13696998.2024.2400856

In this Shortcast, Dr Aya Amer presents the New Zealand experience of using ketone (D,L-3-HB) supplementation in 12 patients (aged 10-50 years) with GLUT1DS.

D,L-3-hydroxybutyrate in the treatment of glucose transporter 1 deficiency syndrome (Glut1DS)

Aya Amer, et al

https://doi.org/10.1002/jmd2.12461

Marshall Summar explains why common polymorphisms and basic physiology mean that L-citrulline may have a role in sickle cell disease, bronchopulmonary dysplasia and even asthma.

Potential therapeutic uses of L-citrulline beyond genetic urea cycle disorders

Marshall Summar

https://doi.org/10.1002/jimd.12810