JIMD Lawrence

Authors Dr Kim Hemsley and Nazzmer Nazri, from the Childhood Dementia Research Group, are joined by their colleague Dr Nick Smith to discuss their recent paper, as well as the wider implications of heterozygosity for Lysosomal Storage Disorders (LSDs) and whether these are associated with early-onset neurodegenerative disease. 50000 children a year are born with conditions associated with childhood dementia and as many as 1 in 40 people carry mutations associated with LSDs so the implications of their work are potentially very wide-ranging.

Is SGSH heterozygosity a risk factor for early‐onset neurodegenerative disease?
Meghan L. Douglass et al.
https://doi.org/10.1002/jimd.12359

LSD Heterozygosity and Neurodegenerative Disease

Professor Judith Fridovich-Keil has been researching galactosemia for over 20 years and it was a privilege to welcome her to the JIMD podcast. The Professor and one of her former lab students and now medical student, Jessica MacWilliams, discuss the promise of new treatments, what drives their interest in galactosemia and a new method for formally assessing fine motor control in these patients.

A pilot study of neonatal GALT gene replacement using AAV9 dramatically lowers galactose metabolites in blood, liver, and brain and minimizes cataracts in GALT‐null rat pups
Shauna A. Rasmussen et al.
https://doi.org/10.1002/jimd.12311

Hand fine motor control in classic galactosemia
Jessica MacWilliams et al.
https://doi.org/10.1002/jimd.12376

Galactosemia: An old diagnosis with new ideas

Professor Robin Lachmann of the Charles Dent Metabolic Unit discusses the science behind Enzyme Replacement Therapy and Gene Therapy and explains why these do, and sometimes do not, work in Lysosomal Storage Disorders. Professor Lachmann also discusses the progress towards establishing adult metabolic services in the UK and elsewhere.

Treating lysosomal storage disorders: What have we learnt?
Robin H. Lachmann
https://doi.org/10.1002/jimd.12131

Education and training in adult metabolic medicine: Results of an international survey
Annalisa Sechi, et al
https://doi.org/10.1002/jmd2.12044

Treatment In Lysosomal Storage Disorders

Melissa Broeks speaks with the podcast about her recent paper reviewing disorders of the malate aspartate shuttle, an essential pathway supporting respiratory chain activity. Melissa provides a wonderful overview of the background and clinical significance of the MAS, all of which can be explored further in her #openaccess paper.

Inborn disorders of the malate aspartate shuttle
Melissa H. Broeks, et al 
https://doi.org/10.1002/jimd.12402

Inborn Errors of the Malate Aspartate Shuttle

In the latest podcast we've returning guest Professor Thorsten Marquardt and his colleague Dr Jörn Oliver Sass talking about their work with 3-Hydroxyisobutyrate dehydrogenase deficiency. Thorsten reports their success in using a low valine diet for an affected patient and Oliver discusses the challenge of differentiating disorder metabolism from disease. 

3-Hydroxyisobutyrate dehydrogenase (HIBADH) deficiency—A novel disorder of valine metabolism
Melanie Meyer et al
https://doi.org/10.1002/jimd.12410

Disease Or Disorder: New Insights in Valine Degradation

Dr Marc Patterson and Dr Eugen Mengel explain the challenges of treating Niemann Pick Type C. Recent studies have shown the efficacy of Miglustat and Arimoclomol but they may end up forming just part of the puzzle being built to manage this condition.

Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment
Eugen Mengel, et al
https://doi.org/10.1002/jimd.12428

Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: A large retrospective observational study
Marc C. Patterson, et al
https://doi.org/10.1002/jimd.12245

Assembling the treatment puzzle in Niemann Pick C

The podcast is joined by the wonderful Dr Sander Houten and Dr Pablo Ranea-Robles who explain their recent working looking at the ATP binding cassette ABCD3 in dicarboxylic fatty acid metabolism.

The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis
Pablo Ranea-Robles et al
https://doi.org/10.1002/jimd.12440

Easy as ABC...D3

Associate Professor Sabine Fuchs and PhD Candidate Vivian Lehmann join the podcast to explain cholangiocyte organoids and the role they play in understanding rare disease and testing new treatments.

The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism
Vivian Lehmann, et al
https://doi.org/10.1002/jimd.12450

Organoids in IMD

This podcast is focused on the paper "Serum ammonia use: unnecessary, frequent and costly”, published online in Frontline Gastroenterology in August 2021. Dr Oliver Tavabie, Trainee Associate Editor of FG and Hepatology SpR at the Royal London Hospital, interviews the authors Drs Elizabeth Aby, Andrew Olson and Nicholas Lim, from the University of Minnesota.
Read the paper on the Frontline Gastroenterology website: https://fg.bmj.com/content/early/2021/08/17/flgastro-2021-101837.
Listen to our regular podcasts and subscribe in Apple Podcasts, Google Podcasts, Stitcher and Spotify.

Serum ammonia use: unnecessary, frequent and costly

Dr Ashish Gupta and Dr Rene Pierpont of the University of Minnesota discuss their work looking at neurocognitive outcomes after transplant in childhood cerebral adrenoleukodystrophy.

Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy
Ashish O. Gupta, et al
https://doi.org/10.1002/jimd.12435

Transplant Outcomes in X-ALD

Dr Sema Kalkan Uçar discusses her observations around two siblings with galactose mutarotase deficiency. Available open access at the link below. 

Two siblings with galactose mutarotase deficiency: Clinical differences
Havva Yazici, et al
https://doi.org/10.1002/jmd2.12263

Shortcast: Two siblings with galactose mutarotase deficiency: Clinical differences

Professor Judy Fridovich-Keil discusses her work looking at acute and developmental outcomes in infants and young children with Duarte galactosemia. 

Acute and early developmental outcomes of children with Duarte galactosemia
Judith L. Fridovich-Keil, et al
https://doi.org/10.1002/jmd2.12267

Shortcast: Acute and early developmental outcomes of children with Duarte galactosemia

Dr Ronen Spiegel and Dr Bernd Schwahn join the podcast to discuss their natural history study in Molybdenum cofactor deficiency and the promise of treatment with cPMP for individuals with MoCD-A. 

Molybdenum cofactor deficiency: A natural history
Ronen Spiegel, et al
https://doi.org/10.1002/jimd.12488

Molybdenum Cofactor Deficiency

Ashley Hertzog discusses the identification of an unexpected promoter variant as a cause of late-onset OTC deficiency.

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency
Ashley Hertzog, et al
https://doi.org/10.1002/jmd2.12289

Shortcast: A serendipitous journey to a promoter variant in OTC

Dr David Olsson discusses the Swedish experience following the introduction of newborn screening for VLCAD deficiency.

Very long-chain acyl-CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics
David Olsson, et al
https://doi.org/10.1002/jmd2.12268

Shortcast: Very long-chain acyl-CoA dehydrogenase deficiency in a Swedish cohort

Professor Bindoff and Professor Gorman, two luminaries of the world of mitochondrial medicine, speak with James Nurse about recent work in JIMD expanding knowledge on safe drug use in Primary Mitochondrial Disease. Professor Bindoff also explains a proposed classification for Polymerase Gamma disease including when to suspect this condition and how to investigate it.

Safety of drug use in patients with a primary mitochondrial disease: An international Delphi‐based consensus
Maaike C. De Vries et al
https://doi.org/10.1002/jimd.12196

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases
Omar Hikmat et al
https://doi.org/10.1002/jimd.12211

Mitochondria, medication and POLG

Dr Michio Hirano and Dr Rita Rinaldi discuss their recent work that summarises a 2 day consensus conference to provide guidance on the diagnosis, prognosis and treatment of Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network
Michio Hirano et al.

https://doi.org/10.1002/jimd.12300

Taking a position on MNGIE

The journal recently published two articles on TANGO2 deficiency, describing a  case series of 20 patients and exploring the uncertain pathophysiology of this condition. Dr Sebastian Montealgre, Dr Pascale de Lonlay, Dr Felix Distelmaier and Dr Michael Sacher joined our social media editor to explain what they observed and the implications of those findings.

Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect
Claire‐Marine Bérat et al. 
https://doi.org/10.1002/jimd.12314

The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER‐to‐Golgi transport and at the mitochondria
Miroslav P. Milev et al. 
https://doi.org/10.1002/jimd.12312

It takes two to TANGO2

Peter Clayton, Emma Footitt and Curtis Coughlin join us to discuss the new consensus guidelines for PDE-ALDH7A1 disease. Professor Clayton explains the pathophysiology and history of the condition. Dr Footitt and Dr Clayton discuss the metabolic investigations of early onset seizures as well as the proposed management of pyridoxine-dependent epilepsy.

Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
Curtis R. Coughlin et al.
https://doi.org/10.1002/jimd.12332

Pyridoxine-dependent epilepsy

In the 16th podcast from the Journal of Inherited Metabolic Disease, Dr Stephan Kemp and Dr Eric Mallack join our social media editor to discuss their recent papers on X-linked adrenoleucodystrophy. Dr Kemp explains how a variety of model systems are used to aid disease understanding and help in the development of new therapies, whilst Dr Mallack shares new guidance around surveillance for the onset of cerebral ALD in childhood.

MRI surveillance of boys with X‐linked adrenoleukodystrophy identified by newborn screening: Meta‐analysis and consensus guidelines
Eric J. Mallack et al.
https://doi.org/10.1002/jimd.12356

Evolution of adrenoleukodystrophy model systems
Roberto Montoro et al.
https://doi.org/10.1002/jimd.12357

JIMD Lawrence

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