In this episode, Dr Gepke Visser, Dr Sacha Ferdinandusse and (soon to be Dr) Marit Schwantje discuss the Netherlands' experience of disorders of MTP activity detected on newborn screening. They also shed light on late-presenting disease phenotypes related to thermo-sensitivity. Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands Marit Schwantje, et al https://doi.org/...
Aug 05, 2022•18 min
Edwin Kirk from the the Australian Reproductive Genetic Carrier Screening Project, discusses the challenges of implementing screening both prior to and during pregnancy. Edwin would like to acknowledge the many international experts who have helped with variant classification, particularly in relation to the PMM2 variant mentioned in the podcast, and in particular would like to thank Belén Pérez and her team for their generosity in performing the functional assays. Reproductive genetic carrier s...
Jul 29, 2022•21 min
Dr Pierre-Axel Monternier discusses his group's work looking at a modified form of the drug pioglitazone to treat X-linked adrenaleukodystrophy. Therapeutic potential of deuterium-stabilized (R)-pioglitazone—PXL065—for X-linked adrenoleukodystrophy Pierre-Axel Monternier, et al https://doi.org/10.1002/jimd.12510
Jul 22, 2022•9 min
Professor Manuel Schiff joins podcast host James Nurse to discuss a recent study looking at the successful use of Betaine in the management of early-onset MTHFR deficiency. Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency Mathilde Yverneau, et al (2022) https://doi.org/10.1002/jimd.12504 Interested listeners may also want to read: Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cbl...
Jul 15, 2022•13 min
Dr Sema Kalkan Uçar returns to the shortcast to present a cohort of 15 patients with MNGIE disease, including 9 with the p.P131L (c.392 C > T), or “Mediterranean” variant. Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy Sema Kalkan Uçar, et al https://doi.org/10.1002/jmd2.12315
Jul 13, 2022•4 min
Dr Xiping Cheng joins podcast host James Nurse to explain her group's work exploring how glutaminase 2 knockdown could provide an alternative approach to management in Urea Cycle Disorders. Glutaminase 2 knockdown reduces hyperammonemia and associated lethality of urea cycle disorder mouse model Xia Mao, et al https://doi.org/10.1002/jimd.12474
Jul 01, 2022•8 min
A team effort as Demi Beneru, Michel Tchan and Kate Billmore explain how they successfully supported a mother with GSD IIIa during her pregnancy. Glycogen storage disease type IIIa in pregnant women: A guide to management Demi Beneru, Michel C. Tchan, Kate Billmore, Roshini Nayyar https://doi.org/10.1002/jmd2.12282
Jun 21, 2022•5 min
Robin Lachmann and Marc Patterson return to the podcast and are joined by their collaborator Dr Sandra Sirrs, to talk about their recent Editorial on drug development in rare disease. Lost in translation—Challenges in drug development for inherited metabolic diseases Robin H. Lachmann, Marc C. Patterson, and Sandra Sirrs https://doi.org/10.1002/jimd.12501
Jun 17, 2022•34 min
Elaine Zaunseder and Dr Ulrike Mütze join the podcast to discuss the role of machine learning in newborn screening and why this is something clinicians need to know about. Opportunities and challenges in machine learning-based newborn screening—A systematic literature review Elaine Zaunseder, et al https://doi.org/10.1002/jmd2.12285
Jun 03, 2022•17 min
The second half of our Barth Syndrome special issue tie in podcast features guest presenter Erik Lontok of the Barth Syndrome Foundation. The podcast looks at the work of Fred Vaz, Bill Pu, Jan Dudek, Christophe Maack and Adam Chicco, all of whom are working to advance our knowledge of Barth Syndrome. Skip to specific papers at the timing below: Dr Fred Vaz, from 2 minutes Dr Bill Pu, from 14 minutes Dr Christophe Macao and Dr Jan Dudek, from 21:45 Dr Adam Chicco, from 31 minutes, 50 seconds. Fe...
May 20, 2022•48 min
In the first of two podcast intended to complement the January 2022 special issue, Dr Hilary Vernon joins the podcast to discuss the clinical presentation and natural history of Barth Syndrome and explore current and future treatments. Clinical presentation and natural history of Barth Syndrome: An overview Carolyn Taylor, et al https://doi.org/10.1002/jimd.12422 Current and future treatment approaches for Barth syndrome Reid Thompson, et al https://doi.org/10.1002/jimd.12453
May 20, 2022•14 min
In honour of CDG Awareness Day, Dr Hudson Freeze and Dr Jaak Jaeken revisit a discussion from the Scientific CDG Symposium 2021, considering what makes a Congenital Disorder of Glycosylation. CDG or not CDG Hudson H. Freeze, Jaak Jaeken and Gert Matthijs https://doi.org/10.1002/jimd.12498
May 16, 2022•18 min
Dr Cindy Towns presents seven cases of HCP from a single family with a novel mutation who have exhibited an unusually high penetrance and high rates of severe, recurrent attacks. High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria Cindy Towns, et al https://doi.org/10.1002/jmd2.12281
May 10, 2022•6 min
Inherited Metabolic Diseases may have both a direct and indirect on dentition resulting on a number of challenges for parents, carers, clinicians and dentists when it comes to managing this. Dr Lorna Hirst and Dr Anupam Chakrapani join the podcast to explain what some of these issues are and why dentists should not be intimidated by IMD patients. Inborn errors of metabolism and their impact in paediatric dentistry Lorna Hirst, Anupam Chakrapani, Suhaym Mubeen https://doi.org/10.1002/jimd.12493
May 06, 2022•18 min
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
May 02, 2022•5 min
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
Apr 28, 2022•4 min
Dr Rebecca Levy of the Lucile Packard Children's Hospital in Stanford, joins the podcast to discuss her recent work looking at epilepsy in NGLY1 deficiency. Delineating the epilepsy phenotype of NGLY1 deficiency Rebecca J. Levy, et al https://doi.org/10.1002/jimd.12494
Apr 22, 2022•11 min
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
Apr 08, 2022•15 min
Dr Maria Fuller explains the clinical utility of the biomarker Chondrotin sulfate disaccharide in the diagnosis of MPSIVA. Chondroitin sulfate disaccharide is a specific and sensitive biomarker for mucopolysaccharidosis type IVA Sharon J. Chin, et al https://doi.org/10.1002/jmd2.12132
Apr 05, 2022•4 min
Dr Kristin Ørstavik explains her team's observations of three patients with a novel mutation in the HADHB gene leading to a mild form of FTP deficiency. Novel mutations in the HADHB gene causing a mild phenotype of mitochondrial trifunctional protein (MTP) deficiency Kristin Ørstavik, et al https://doi.org/10.1002/jmd2.12276
Apr 01, 2022•4 min
Professor Ranganath returns to the podcast and is joined by Dr Nick Sireau to discuss the SONIA 2 study, getting the Nitisinone dose right and how we should manage alkaptonuria in children. Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling Lakshminarayan R. Ranganath, et al https://doi.org/10.1002/jmd2.12261 Effects of a protein-restricted diet on body weight and serum tyrosine concentrations in patients with alkaptonuria Birgitta Olsson...
Mar 25, 2022•26 min
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
Mar 15, 2022•7 min
Dr George Diaz and Dr Spyros Batzios join the podcast to discuss a slight more unusual UCD, Arginase deficiency. They discuss the clinical features of the condition, the current management and a promising new therapy. Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency Nandaki Keshavan, et al https://doi.org/10.1002/jmd2.12266 Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency George A. Diaz, et al h...
Mar 11, 2022•13 min
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
Mar 04, 2022•3 min
Dr Megan Brophy and Dr Bob Bell join the podcast to talk about their recent work looking at AAV gene therapy in fibroblasts from patients with classic galactosemia. We discuss new insights into disease physiology and consider the challenges of scaling gene therapy towards in vivo model. AAV-mediated expression of galactose-1-phosphate uridyltransferase corrects defects of galactose metabolism in classic galactosemia patient fibroblasts Megan L. Brophy, et al https://doi.org/10.1002/jimd.12468
Feb 25, 2022•13 min
Vicente Rubio, Belén Pérez, Santiago Ramón-Maiques join the podcast to discuss their recent work analysing the crystal structure of PMM2 and the insights this provides towards developing new treatments. Insight on molecular pathogenesis and pharmacochaperoning potential in phosphomannomutase 2 deficiency, provided by novel human phosphomannomutase 2 structures Alvaro Briso-Montiano, et al https://doi.org/10.1002/jimd.12461
Feb 11, 2022•21 min
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
Jan 27, 2022•19 min
The first podcast of 2022 discusses two papers with negative outcomes and explores the importance of sharing such results for patients and families and clinicians working with rare disease. Dr Nicoline Løkken discusses her work with resveratrol in mitochondrial myopathies (from 5m 18s) and Dr Arunabha Ghosh and Professor Brian Bigger talk about the use of genistein in Sanfilippo syndrome (from 10m 38s). No effect of resveratrol in patients with mitochondrial myopathy: A cross-over randomized con...
Jan 14, 2022•30 min
Dr Gabriele Ramoser, Dr Federica Caferri, Dr Sabine Scholl-Bürgi and Dr Daniela Karall joined the podcast to discuss their recent work looking at the Austrian "Registry for Inherited Metabolic Disorders". We spoke about the importance of patient registries, variable prevalence rates and the difficulties around where to care for adults with IMD. 100 years of inherited metabolic disorders in Austria—A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors o...
Dec 31, 2021•14 min
In March 2021 our special issue look at all aspects of Mitochondrial Disease. In this special episode Professor Shamima Rahman guest hosts as we welcome David Dimmock, Mike Lawlor, Guilhian Leipnitz and Marc Patterson to discuss their papers from that issue, looking at novel therapies in mitochondrial disease. For those skipping: DGUOK (from 3min 30sec), SO deficiency (from 19min) and Friedreich's Ataxia (29min 10sec). The nucleotide prodrug CERC-913 improves mtDNA content in primary hepatocytes...
Dec 17, 2021•41 min
