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 a…

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 studyLucas Agnoletto, …

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.…

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 assessmentAsthik Biswas, et alhttps://doi.org/1…

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 glycosyla…

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 yea…

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 alhttps://doi.org/10.1002/jmd2.12461By Journal of Inherited Metabolic Disease

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 disordersMarshall Summarhttps://doi.org/10.1002/jimd.12810…

Dr Ashlee Stiles discusses the work-up of a 13-month-old girl with hypoglycaemia and discusses the need to balance prompt metabolic work-up with managing the acutely unwell patient in front of you. Critical sample collection is key and don't forget the urine. Read the report here: https://www.sciencedirect.com/science/article/pii/S2214426924000156?…

In this Metabolic Mystery, Dr Eamon McCarron unravels an unexpected diagnosis in a 55-year-man with a 2-year history of dragging his legs, poor balance, and paresthesia along the outer aspect of his right thigh. He underwent various assessments and investigations over the next 3 years before a diagnosis was made. https://onlinelibrary.wiley.com/doi…

Dr Jessica Gold discusses observations around executive function in early treated MSUD patients and how this impacts on outcomes around transition to adulthood. Executive and adaptive function impacts long-term outcomes for adults with maple syrup urine diseaseJessica I. Gold, et alhttps://doi.org/10.1002/jimd.12827…

Dr Thomas Cassini explains how the Undiagnosed Diseases Network group used advanced sequencing techniques to clarify the genotype in a child with an unusual phenotype for mitochondrial trifunctional protein deficiency.Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicingThomas Cassini, et alh…

Dr Andrew Morris joins the podcast to discuss insights from 311 patients with CBS deficiency (classical homocystinuria), their response to treatment and clinical outcomes. Cystathionine β-Synthase Deficiency in the E-HOD Registry—Part II: Dietary and Pharmacological TreatmentAndrew A. M. Morris, Jitka Sokolová, Markéta Pavlíková, Florian Gleich, St…

Eva Hoytema van Konijnenburg and Clara van Karnebeek tell the podcast about the treatabolome an epic project to include all current IMD treatments and add them to the IEMbase. The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!Bibiche den Hollander, et alhttps://doi.org/10.100…

Nathalie Guffon joins the podcast to discuss alpha-mannosidosis and the long term efficacy of enzyme replacement therapy with velmanse alfa.Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosisNathalie Guffon, et alhttps://doi.org/10.1002/jimd.12799…

It seems everyone is talking about autophagy but what is it and what happens when it goes wrong? Hormos Salimi Dafsari, Carlo Dionisi-Vici, and Heinz Jungbluth join the podcast to answer these questions, discuss their experience across 3 (or 2.5) generations of clinical practice and why you never see an obese 100-year-old.An update on autophagy dis…

Marie-Thérèse Henke, Alessandro Prigione, and Markus Schuelke get 2025 off to an informative start discussing why so many models exist for Leigh Syndrome, why we need them and how insights from disease models have led to Sildenafil being used in some patients. Disease models of Leigh syndrome: From yeast to organoidsMarie-Thérèse Henke, Alessandro …

Dr François Feillet returns to the podcast to discuss the final results of the KAMPER study, evaluating the long-term safety of sapropterin in phenylketonuria (phenylalanine hydroxylase deficiency).Long-term safety of sapropterin in paediatric and adult individuals with phenylalanine hydroxylase deficiency: Final results of the Kuvan® Adult Materna…

Dr Sema Kalkan Uçar joins the podcast to discuss the merits of a high protein, high fat diet for the management of patients with Glycogen Storage Disease type 3a.Long-term personalized high-protein, high-fat diet in pediatric patients with glycogen storage disease type IIIa: Evaluation of myopathy, metabolic control, physical activity, growth, and …

Dr Gabriella Horvath returns for her second visit to the podcast, joining Eva Morava to discuss psychiatric presentations of Inherited Metabolic Disease.Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2020.02.007Find IMDs associated with psychiatric presentations at: http://iembase.org/gamuts/store/docs/Psychiatric_IMD_gamuts.pdf…

In this Shortcast Antonio Ochoa-Ferraro and Dr Charlotte Dawson share their experience using the medication Volanesorsen with two pregnant women diagnosed with familial chylomicronemia syndrome.Two successful pregnancies in patients taking Volanesorsen for familial chylomicronemia syndromeSubadra Wanninayake, et alhttps://doi.org/10.1002/jmd2.12435…

In the latest podcast, Dr Lourdes Desviat provides an overview of the different RNA based therapeutic approaches including how they work and which are showing promise for the management of Urea Cycle Disorders. Exploring RNA therapeutics for urea cycle disordersEva Richard, Ainhoa Martínez-Pizarro, Lourdes R. Desviathttps://doi.org/10.1002/jimd.128…

Dr Hannerieke van den Hout of Erasmus MC joins the podcast to discuss observations from two decades of early treated infantile onset Pompe disease and the evolving nature of the neurological phenotype.Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive …

Callie Ferguson discusses her group's care for a young woman with FBPase deficiency during pregnancy and beyond. Metabolic management of a successful pregnancy and postpartum complications in fructose-1,6-bisphosphatase deficiencyCallie Ferguson, Anita Madison, Ada Hamosh, Celide Koernerhttps://doi.org/10.1002/jmd2.12453…

Professor Shamima Rahman and Dr Nandaki Keshavan take us on a whistle stop tour of the different approaches taken to gene therapy in mitochondrial disease and why some may work better than others. Gene therapy for mitochondrial disordersNandaki Keshavan, Michal Minczuk, Carlo Viscomi, Shamima Rahmanhttps://doi.org/10.1002/jimd.12699…

Olivia Garrett, Jared Druss, Estela Rubio-Gozalbo, Gerard Berry, and Judith Fridovich-Keil discuss outcomes in classic galactosemia drawn from patient surveys of 92 adults.Health and well-being of maturing adults with classic galactosemiaOlivia S. Garrett, Jared J. Druss, E. Naomi Vos, Yu-Ting Debbie Fu, Stephanie Lucia, Patricia E. Greenstein, Ann…

Professor Carlos Ferreira joins Eva Morava to discuss the metabolic cardiovascular disease and explain why cardiac involvement is common in IMDs and when an underlying metabolic should be suspected in a cardiac presentation.Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2020.12.290Find IMDs associated with epilepsies at: http://www…

Originally presented at the SSIEM 2023 Annual Symposium, Dr Ozlem Goker-Alpan discusses neuronopathic gaucher disease, regional variations and hopes for new treatments.Neuronopathic Gaucher disease: Rare in the West, common in the EastOzlem Goker-Alpan, Margarita M. Ivanovahttps://doi.org/10.1002/jimd.12749…

Dr Melanie Gillingham, PhD, RD, joins the podcast to discuss eye disease in LCHADD and changes in outcomes following early or late diagnosis. Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathyMelani…

Professor Corrado Angelini joins Eva Morava to discuss the footprints of metabolic myopathies, why they are so common and when they should be suspected. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2022.09.004Find IMDs associated with epilepsies at: http://www.iembase.org/gamuts/store/docs/Footprints_myopathies_table%20151022.pdf…

Professor Judy Fridovich-Keil returns to the podcast to explain her work to illustrate whether the phenotype of galactosemia is related to GALT activity or galactose metabolism. Her group have been working with plant enzymes in fruit flies. Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adul…

Dr Roman Trepp attempts to answer the question, Do early-treated adults with phenylketonuria sense high phenylalanine levels?Do early-treated adults with phenylketonuria sense high phenylalanine levels?Laura Hauri, Raphaela Muri, Regula Everts, Roman Trepphttps://doi.org/10.1002/jmd2.12446By Journal of Inherited Metabolic Disease

Professors Fréd Vaz and Ronald Wanders present an entertaining and informative overview of fatty acid homeostasis and explain why the catabolic and anabolic processes cannot be considered separately.Disorders of fatty acid homeostasisFrédéric M. Vaz, et al https://doi.org/10.1002/jimd.12734By Journal of Inherited Metabolic Disease

Dr Annet Bosch describes three cases where young adults developed worsening neurological symptoms after a change in diet. Initially confused with Guillan-Barré Syndrome, this treatable condition may be hard to diagnose but devastating to miss. Find full details here: https://doi.org/10.1002/jmd2.12427…

Dr Irena Muffels is joined by Professor Eva Morava to discuss insights into heterozygous DHDDS variants, an autosomal dominant IMD that appears to impact on multiple different metabolic pathways. Assessing age of onset and clinical symptoms over time in patients with heterozygous pathogenic DHDDS variantsI. J. J. Muffels, et alhttps://doi.org/10.10…

Professor Phillip Pearl joins Eva Morava to discuss the footprints of metabolic epilepsies and a very brief introduction to the intertwined nature of music and neurology. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2023.107690Find IMDs associated with epilepsies at: http://iembase.org/gamuts/store/docs/IMDs_presenting_with_epile…

Dr Henry Lee joins the podcast to discuss the challenges of developing gene therapies for inherited disorders of neurotransmission and shares the progress that his group has made with SSADH deficiency. Gene replacement therapies for inherited disorders of neurotransmission: Current progress in succinic semialdehyde dehydrogenase deficiencyHenry H. …

Dr Tom Hartl discusses his group's work with a mouse model that knocks out both GALT and GALK and the insights that this provides into classic galactosemia.Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemiaLinley Mangini, et alhttps://doi.org/10.1002/jmd2.12…

Marjorie Dixon and Annemiek van Wegberg join guest host Curtis Coughlin II to complete the treatment puzzle in pyridoxine dependent epilepsy and explain the role and practicalities of lysine restriction in PDE.Dietary management for pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency, a follow-on from the intern…

Nenad Blau hosts Professor David Cassiman as he explains when to consider a metabolic differential in pediatric and adult liver disease. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2019.04.002Find liver disorders associated with IMDS at: http://iembase.org/gamuts/store/docs/Liver_disorders_in_inherited_metabolic_disorders.pdf…

In the latest shortcast, Inez Bosnyak describes a case of ALG1-CDG presenting without an abnormal isoelectric focusing pattern. Normal transferrin glycosylation does not rule out severe ALG1 deficiencyInez Bosnyak, et alhttps://doi.org/10.1002/jmd2.12415By Journal of Inherited Metabolic Disease

Dr Estela Rubio-Gozalbo and Dr Bernadette Jansma explain why brains oscillate, what that has to do with classical galactosemia and how a non-invasive intervention could help with language difficulties. Altered neural oscillations in classical galactosaemia during sentence productionSara Mazzini, et alhttps://doi.org/10.1002/jimd.12740Impact of thet…

Alexandre Nguyen and Manuel Schiff share the story of two siblings with severe haemolytic anaemia developing in previously well controlled methionine synthase reductase deficiency.Late-onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose e…

Dr Fanny Mochel returns to the podcast to answer the question, "What can pediatricians learn from adult inherited metabolic diseases?"Based on a talk at the SSIEM 2023 Annual Symposium.What can pediatricians learn from adult inherited metabolic diseases?Fanny Mochelhttps://doi.org/10.1002/jimd.12729By Journal of Inherited Metabolic Disease

Dr Vykunta Raju K N, Professor of Paediatric Neurology discusses a child presenting with IUGR, microcephaly, cataracts, developmental delay, seizures, and cerebral atrophy.L-Serine Biosynthesis Defect: A Treatable Condition Masquerading as TORCH InfectionVykuntaraju K. Gowda et alhttps://link.springer.com/article/10.1007/s12098-024-05181-3…

Eva Morava discusses the creation of the IEMbase with Nenad Blau before the pair welcome Gabriella Horvath to discuss metabolic mimics of cerebral palsy in the first episode of the footprints series. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2021.03.008Find all the metabolic mimics of CP at http://iembase.org/gamuts/store/docs…

Dr Maja Risager Nielsen and Dr François Feillet discuss pregnancy in PKU and two different papers looking at the outcomes in pregnancies with and without BH4 treatment. The impact of phenylalanine levels during pregnancy on birth weight and later development in children born to women with phenylketonuriaMaja Risager Nielsen, et alhttps://doi.org/10…

When might acute liver failure have a metabolic cause? Dr Robert Hegarty tries to answer this question and more following his recent review article on Genetic aetiologies of acute liver failure.Genetic aetiologies of acute liver failureRobert Hegarty, Richard J. Thompsonhttps://doi.org/10.1002/jimd.12733…

Dr Mariko Bennett and Dr Laura Adang discuss the precarious balance between a protective and a destructive immune response, as is seen in inborn errors in nucleotide metabolism. Our discussion focuses on the most common of these disorders: Aicardi Goutières syndrome (AGS). Sadly, despite the many gains in understanding about AGS, there remain many …

Dr Gustavo Spolador discusses the paucity of data around palliative care in Inherited Metabolic Disease and some of his own observations in a Brazilian quaternary hospital.Pediatric palliative care for metabolic diseases: 20-year epidemiological survey of outpatients at a Brazilian quaternary hospitalGustavo Marquezani Spolador, et alhttps://doi.or…