The podcast returns to the subject of gene therapy, with Julien Baruteau, Nicola Brunetti-Pierri, and Paul Gissen discussing the potential of liver directed therapies with an emphasis on Wilson disease, Crigler-Najjar syndrome and PKU. Liver-directed gene therapy for inherited metabolic diseases Julien Baruteau, Nicola Brunetti-Pierri, Paul Gissen https://doi.org/10.1002/jimd.12709
Dr Maren Thiel, Chair of the German speaking self-help group for fatty oxidation disorders, presents work completed with the Freiburg metabolic team looking at psychosocial issues and coping strategies in families affected by LC-FAOD. Psychosocial issues and coping strategies in families affected by long-chain fatty acid oxidation disorders Maren Thiel, et al https://doi.org/10.1002/jmd2.12402
Listener feedback link: https://form.jotform.com/240459204544050 Kunwar Jung-KC and Alba Tristán-Noguero discuss tyrosine hydroxylase deficiency and explain how the tyrosine hyodroxylase cofactor, BH4, has shown early therapeutic potential in human neurons and a knock-in mouse model. Tetrahydrobiopterin (BH4) treatment stabilizes tyrosine hydroxylase: Rescue of tyrosine hydroxylase deficiency phenotypes in human neurons and in a knock-in mouse model Kunwar Jung-KC, Alba Tristán-Noguero, et al ht...
Dr Hiroki Hanafusa presents the unusual case of a woman who was initially diagnosed with Fanconi Syndrome and later found to have Lysinuric Protein Intolerance. Lysinuric protein intolerance exhibiting renal tubular acidosis/Fanconi syndrome in a Japanese woman Hiroaki Hanafusa, et al https://doi.org/10.1002/jmd2.12392
A superlative trio, Dr Machteld Oud, Dr Clara van Karnebeek and Dr Saskia Wortmann join the podcast to explain the importance of diagnostics, why all exomes aren't equal and just how should you proceed after a 'negative' exome. How to proceed after “negative” exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques Saskia B. Wortmann, et al https://doi.org/10.1002/jimd.12507
Merel Hermans describes her work reviewing neuropsychological stability in adults with classical galactosemia. Neuropsychological stability in classical galactosemia: A pilot study in 10 adult patients Merel E. Hermans, et al https://doi.org/10.1002/jmd2.12410
Returning guests, Nina Stolwijk and Dr Carla Hollak, and their colleague Dr Annet Bosch, try to untangle the tricky subject of regulation in nutritional products used as therapies in IMD. They also present a framework for when a food should be considered a medicine. Food or medicine? A European regulatory perspective on nutritional therapy products to treat inborn errors of metabolism N. N. Stolwijk, et al https://doi.org/10.1002/jimd.12677
Shelby Mills on behalf of the UTH Medical Genetics Team, invites you to consider three mystery cases serving to hi-light some common, and some less common, presenting features for a treatable inherited metabolic disease. Arginase deficiency masked by cerebral palsy and coagulopathy—Three varied presentations of Latin American origin Shelby L. Mills, et al https://doi.org/10.1002/jmd2.12397
Dr Sonam Gurung and Dr Julien Baruteau discuss movement disorders in Arginosuccinic aciduria and explain how recent work with mRNA therapy shows potential as a treatment in this condition. The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria Gurung et al https://doi.org/10.1002/jimd.12691 mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aci...
Dr Malak Alghamdi unravels the mystery of a 32-year-old woman with a history of recurrent miscarriage and early neonatal death with congenital anomalies. Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman Malak Ali Alghamdi, et al https://doi.org/10.1002/jmd2.12384
In this podcast, Dr Roshni Vara discusses the experience of a single paediatric liver centre with children whose liver failure arose due to a mitochondrial DNA depletion syndrome. Hepatic presentations of mitochondrial DNA depletion syndrome in children: A single tertiary liver centre experience R. Vara, et al https://doi.org/10.1002/jimd.12633
Professor Jayesh Sheth shares 20 years of insights on diagnosing adult onset lysosomal storage disorders at a tertiary genetic centre in India. Lysosomal storage disorders identified in adult population from India: Experience of a tertiary genetic centre and review of literature Jayesh Sheth, et al https://doi.org/10.1002/jmd2.12407
Dr David Bick, Dr Jim Bonham MBE and Henrietta Hopkins re-create a panel from the SSIEM Annual Meeting in 2022 to discuss the use of whole genome sequencing in NBS, asking "are we entering a new era of screening?" Genomic newborn screening: Are we entering a new era of screening? Ute Spiekerkoetter, et al https://doi.org/10.1002/jimd.12650
Dr Sander Houten discusses a child with hyperlysinemia diagnosed via newborn screening and whether this reflects a disease or just a metabolic perturbation. This distinction is relevant as inducing this state may be a treatment option in GA1 or pyridoxine dependent epilepsy. A case of hyperlysinemia identified by urine newborn screening Mehdi Yeganeh, et al https://doi.org/10.1002/jmd2.12399
The Journal of Inherited Metabolic Disease Editorial Committee come together to talk about the direction of metabolic medicine, the dangers and potential of AI, impact factors, reviewing papers and their publication hopes for 2024. There's also a little metabolic quiz, allowing you to pit your wits against the committee. Featuring: Shamima Rahman, Matthias Baumgartner, Verena Peters, Marc Patterson, Johannes Zschocke and Sean Froese. Quo vadis now: Beyond genomics to an era of personalised medic...
Blood spots are integral to disease monitoring in PKU, however, there are concerns regarding correlation between capillary and plasma levels and discrepancies arising based on sampling quality and storage. Dr Rachel Carling explains how a volumetric blood collection device presents a cost effective way to improve consistency and reduce rejected samples. Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devices Rachel S....
In our latest podcast, Antonia Ribes, Frederic Tort, and Gerard Muñoz-Pujol discuss CRISPR/Cas9 based technique for the validation of genetic variants requiring just the genetic data. CRISPR/Cas9-based functional genomics strategy to decipher the pathogenicity of genetic variants in inherited metabolic disorders Gerard Muñoz-Pujol, et al https://doi.org/10.1002/jimd.12681
In the latest Shortcast, Jared J. Druss and Professors Nancy Potter and Judy Fridovich-Keil discuss grip strength in galactosemia (and how competitive boys can bias study results). Grip strength in patients with galactosemia and in a galactose-1-phosphate uridylyltransferase (GALT)-null rat model Jared J. Druss, et al https://doi.org/10.1002/jimd.12684
Dr Dwight Koeberl joins the podcast to provide some background to gene therapies in Glycogen Storage Disorders, hi-light some ongoing studies and explain why we owe at least some of our knowledge to a menagerie of animal models. Gene therapy for glycogen storage diseases Dwight D. Koeberl, et al https://doi.org/10.1002/jimd.12654
Dr Will Heath describes insights form screening data derived from 19 patients enrolled in a phase 1 study in late-onset Pompe disease. Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapy William B. Hannah, et al https://doi.org/10.1002/jmd2.12391
In an ensemble piece, Dr Saskia Wortmann, Dr Hud Freeze, and Dr Santiago Ramón-Maiques discuss CAD deficiency and the challenge of finding new ways to validate genetic variants when pathogenicity seems uncertain. Beyond genetics: Deciphering the impact of missense variants in CAD deficiency Francisco del Caño-Ochoa, et al https://doi.org/10.1002/jimd.12667
Dr Kaustuv Bhattacharya explains the insights of his team into the diagnosis and management of a cohort of children with McArdle Syndrome and challenges some of the conceptions around this disease. Diagnosis and management of children with McArdle Syndrome (GSD V) in New South Wales Louisa Adams, et al https://doi.org/10.1002/jmd2.12389
Dr Rodrigo Starosta describes the management of a challenging presentation of PIGO-CDG and discusses insights into this rare GPI-anchor disorder. PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations Rodrigo Tzovenos Starosta, et al https://doi.org/10.1002/jmd2.12396
It's a 2-for-1 podcast as Dr Mattias Lissing of the Karolinska Institute joins us to discuss two recent papers looking at cancer risk, comorbidity and mortality in the acute porphyrias. Risk for incident comorbidities, nonhepatic cancer and mortality in acute hepatic porphyria: A matched cohort study in 1244 individuals Mattias Lissing, et al https://doi.org/10.1002/jimd.12583 Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case–control study of 188 patie...
Dr Markey McNutt of UT South Western describes a patient presenting with post-partum ataxia and confusion and just when you think you know the answer there's an extra mystery at the end. Read the paper here: https://doi.org/10.1002/jmd2.12388
Dr Claire Horgan discusses the first year of offering gene therapy to patients with metachromatic leukodystrophy (MLD) in the UK. When given in a timely fashion the impact is incredible but large numbers of children remain ineligible for treatment. A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie ahead Claire Horgan, et al https://doi.org/10.1002/jmd2.12378
In this podcast, Dr Kristen Skvorak discusses the development and testing of a new oral enzyme for the treatment of Maple Syrup Urine Disease. Oral enzyme therapy for maple syrup urine disease (MSUD) suppresses plasma leucine levels in intermediate MSUD mice and healthy nonhuman primates Kristen Skvorak, et al https://doi.org/10.1002/jimd.12662
Enzyme Replacement Therapy (ERT) has changed the course of several lysosomal storage disorders but regular, intravenous administration is not without its issues. In this latest Shortcast, Dr Paulina Dabrowska-Schlepp describes her group's work to develop subcutaneous ERT for Fabry Disease. Comparison of efficacy between subcutaneous and intravenous application of moss-aGal in the mouse model of Fabry disease Paulina Dabrowska-Schlepp, et al https://doi.org/10.1002/jmd2.12393
Dr Luisa Averdunk of the University Children's Hospital in Düsseldorf discusses the investigation of a 2-year-old presenting with acute episodes of dystonia and symmetrical basal ganglia abnormalities. Will you unravel this metabolic mystery before all is revealed? See the associated image and read the full report here: https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12680
In our latest podcast we welcome Simon Waddington, Professor in Gene Transfer Technology at the EGA Institute for Women's Health. Professor Waddington discusses the development of fetal gene therapy and why it might be desirable to deliver gene therapy to the unborn child. Fetal gene therapy Simon N. Waddington, et al https://doi.org/10.1002/jimd.12659
