JIMD Podcasts

Dr Samuel Mackenzie discusses the perplexing presentation of a 61-year-old man with rhabdomyolysis and a prolonged QT interval. Further exploration reveals a lifetime of episodic fatigue with illnesses. https://doi.org/10.1016/j.ymgmr.2025.101241

Inherited metabolic diseases aren’t just for the young. James Nurse talks with François Maillot and Ida Schwartz about their systematic review revealing how IMDs can first be diagnosed well into older age. From Fabry disease to alkaptonuria, they discuss diagnostic delays, missed clues, and why it’s time to think about geriatric metabolic medicine. Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review Maria-Rita Moio, et al https://doi.org/10.1002/jimd.70038

With Rodrigo off caring for sick children, James Nurse joins Silvia Radenkovic to speak with Dr Judith Jans and Dr Devin Oglesbee about the emerging field of untargeted metabolomics. Authors’ opinions are their own and do not represent their institutions. Referenced papers include: Miller MJ, et al The emerging role of metabolomics analysis in genetic and genomic testing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jul 17:101493. doi: 10.1016/j.gim.2025.101493. Epub ahead of print. Evans AM, et al Dissemination and analysis of the quality assurance (QA) and quality control (QC) practices of LC-MS based untargeted metabolomics practitioners. Metabolomics. 2020 Oct 12;16(10):113. doi: 10.1007/s11306-020-01728-5. Wurth R, et al. An evaluation of untargeted metabolomics methods to characterize inborn errors of metabolism. Mol Genet Metab. 2024 Jan;141(1):108115. doi: 10.1016/j.ymgme.2023.108115. Epub 2023 Dec 15. Haijes HA, et al. Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma. Metabolites. 2019 Jan 11;9(1):12. doi: 10.3390/metabo9010012. Willems AP, et al A one-year pilot study comparing direct-infusion high resolution mass spectrometry based untargeted metabolomics to targeted diagnostic screening for inherited metabolic diseases. Front Mol Biosci. 2023 Nov 2;10:1283083. doi: 10.3389/fmolb.2023.1283083. Haijes HA, et al. Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation. Mol Genet Metab. 2019 Aug;127(4):368-372. doi: 10.1016/j.ymgme.2019.07.001. Epub 2019 Jul 9. PMID: 31311714. Hoegen B, et al Application of metabolite set enrichment analysis on untargeted metabolomics data prioritises relevant pathways and detects novel biomarkers for inherited metabolic disorders. J Inherit Metab Dis. 2022 Jul;45(4):682-695. doi: 10.1002/jimd.12522. Epub 2022 May 22. PMID: 35546254; PMCID: PMC9544878. Gao Q, et al A diagnostic algorithm for inherited metabolic disorders using untargeted metabolomics. Metabolomics. 2025 Jul 27;21(4):101. doi: 10.1007/s11306-025-02302-7. PMID: 40715884; PMCID: PMC12301266. Kerkhofs MHPM, et al. Cross-Omics: Integrating Genomics with Metabolomics in Clinical Diagnostics. Metabolites. 2020 May 18;10(5):206. doi: 10.3390/metabo10050206. Ashenden AJ, et al. The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges. Int J Neonatal Screen. 2024 Jun 21;10(3):42. doi: 10.3390/ijns10030042. Liu N, et al. Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism. JAMA Netw Open. 2021 Jul 1;4(7):e2114155. doi: 10.1001/jamanetworkopen.2021.14155.

Can small molecules stabilise OTC enzyme activity and change the outlook for urea cycle disorders? Dr Alexander Laemmle (University Hospital Bern) discusses pharmacological chaperones, a novel approach that strengthens enzyme stability in patient-derived liver models and offers new hope for female OTC carriers. Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models Adhuresa Ramosaj, et al https://doi.org/10.1002/jimd.70043 Induced pluripotent stem cell technology as diagnostic tool in patients with suspected ornithine transcarbamylase deficiency lacking genetic confirmation Adhuresa Ramosaj et al https://doi.org/10.1016/j.ymgmr.2023.101007

Shortcast: Clinical and Developmental Outcomes after 50 Years of Galactosaemia NBS in Ireland by Journal of Inherited Metabolic Disease

In this episode we discuss new insights into the variability of long-term outcomes in classic galactosemia. Joining me are Nikki Smith, Olivia Garrett, and Judy Fridovich-Keil, who together explore how complications in cognitive, motor, and speech domains emerge, cluster, and vary in severity across patients. Their study highlights both patterns and unanswered questions, illustrating the challenges families face and the importance of refining prognostic tools. Patterns of Penetrance and Expressivity of Long-Term Outcomes in Classic Galactosemia Nicole H. Smith et al. https://doi.org/10.1002/jimd.70020

Silvia and Rodrigo are joined by Dr Ray Wang, Director of the multidisciplinary Foundation of Caring Lysosomal Storage Disorder Program at the Children's Hospital of Orange County. Silvia asks Dr Wang and Rodrigo (who also happens to be a researcher in this field) about cutting-edge advances in LSD research: from base editing in Pompe disease and patient-specific in vivo gene editing, to new biomarkers and scoring systems in Gaucher disease, insights into lipid dysregulation across lysosomal storage disorders, and the first clinical trial of anakinra in Sanfilippo syndrome. Papers discussed include: Christensen CL, et al Base editing rescues acid α-glucosidase function in infantile-onset Pompe disease patient-derived cells. Mol Ther Nucleic Acids. 2024 May 21;35(2):102220. doi: 10.1016/j.omtn.2024.102220. PMID: 38948331; PMCID: PMC11214518. Starosta RT, et al Predicting liver fibrosis in Gaucher disease: Investigation of contributors and development of a clinically applicable Gaucher liver fibrosis score. Mol Genet Metab. 2025 Feb;144(2):109010. doi: 10.1016/j.ymgme.2025.109010. Epub 2025 Jan 3. PMID: 39788861. Kell P, et al Secondary accumulation of lyso-platelet activating factors in lysosomal storage diseases. Mol Genet Metab. 2025 Jun 17;145(4):109180. doi: 10.1016/j.ymgme.2025.109180. Polgreen LE, et al Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21. Erratum in: Nat Med. 2024 Sep;30(9):2693. doi: 10.1038/s41591-024-03207-z. Musunuru K, et al Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med. 2025 Jun 12;392(22):2235-2243. doi: 10.1056/NEJMoa2504747.

What if one enzyme could link metabolism, epigenetics, and therapy across conditions as diverse as epilepsy, cancer, and inflammation? In this episode, we dive into the fascinating world of adenosine kinase (ADK), an ancient enzyme that controls adenosine levels, energy balance, and even DNA methylation. Dr Detlev Boison join us to discuss their recent review in the Journal of Inherited Metabolic Disease, which reframes ADK not just as a metabolic regulator, but as a potential epigenetic drug target. From seizure suppression to cancer immunology, ADK sits at a crossroads, and could be a future key to metabolic and epigenetic medicine. Adenosine Kinase: An Epigenetic Modulator and Drug Target Uchenna Peter-Okaka, Detlev Boison https://doi.org/10.1002/jimd.70033

The first updated Footprints article requires two guests to do it justice - Dr Dakota Peacock and Dr Darius Ebrahimi-Fakhari join Eva Morava to discuss movement disorders in Inherited Metabolic Disease. Read the referenced paper here: https://doi.org/10.1016/j.ymgme.2025.109084 Find IMDs associated with psychiatric presentations at: https://www.iembase.org/gamuts/store/docs/Movement_disorders_update.pdf

A newborn with no symptoms, an unexpected X-ray finding, and a puzzle that points in many possible directions. Follow Dr. Tolulope Tolufase as he unpacks a neonatal case where incidental adrenal calcifications conceal a far deeper mystery. Read the full report here: https://doi.org/10.1136/bcr-2025-265278

In this episode, we speak with Irena Muffels and Eva Morava about their recent review, The Therapeutic Future for Congenital Disorders of Glycosylation. We explore the three pillars they propose for advancing CDG treatment: improving disease models, enhancing clinical trial readiness, and finding scalable strategies that move us beyond one-gene-at-a-time approaches. From patient-derived brain organoids to AI-powered outcome assessments and the promise of basket trials, this conversation is a sweeping tour through the innovations shaping the future of CDG care. The Therapeutic Future for Congenital Disorders of Glycosylation I. J. J. Muffels, T. Kozicz, E. O. Perlstein, E. Morava https://doi.org/10.1002/jimd.70011

In this episode, Prof Chris Vorster (Director, Centre for Human Metabolomics, North-West University, South Africa), Sarah Viall (Assistant Professor, Molecular and Medical Genetics, Oregon Health & Science University, USA) and PD Dr. med. Ulrike Mütze (Consultant, Heidelberg University Hospital, Germany) join Silvia Radenkovic and Rodrigo Starosta to explore the evolving landscape of newborn screening. They discuss national and international variations in practice, how to maintain consistency and quality, and the future scope of testing – including opportunities to improve access in resource-limited settings. Authors’ opinions are their own and do not represent their institutions. Referenced papers include: Newborn screening in South Africa: the past, present, and plans for the future. Malherbe et al (2024) Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. McHugh et al (2024) Five years of newborn screening for Pompe, Mucopolysaccharidosis type I, Gaucher, and Fabry diseases in Oregon. Viall & Held (2025) Long-term outcomes of adolescents and young adults identified by metabolic newborn screening. Mütze et al (2025) Treatment Outcomes for Maple Syrup Urine Disease Detected by Newborn Screening. Mengler et al (2024) Vitamin B12 Deficiency Newborn Screening. Mütze et al (2024) The role of exome sequencing in newborn screening for inborn errors of metabolism. Adhikari et al (2020)

In this episode, Sabine Fuchs and Eva Hoytema discuss their recent work exploring the expanding clinical spectrum of aminoacyl-tRNA synthetase deficiencies, highlighting diagnostic challenges and emerging insights into this complex group of rare disorders. Setting the Stage for Treatment of Aminoacyl-tRNA Synthetase (ARS)1-Deficiencies: Phenotypic Characterization and a Review of Treatment Effects Eva M. M. Hoytema van Konijnenburg, et al https://doi.org/10.1002/jimd.70017

Marya Sabir shares new insights into the utility of leukocyte sialic acid levels as a diagnostic and monitoring tool in free sialic acid storage disorder. Investigating the Utility of Leukocyte Sialic Acid Measurements in Lysosomal Free Sialic Acid Storage Disorder Marya S. Sabir, et al https://doi.org/10.1002/jmd2.70029

Dr Laura Adang returns to the podcast, this time discussing diagnostic delays in early onset forms of metachromatic leukodystrophy and explains why the only logical route to prompt diagnosis is newborn screening and how gene therapy might lead to a 'normal' life for children, if only we can find them early enough. Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data Approach Ali Mohajer, et al https://doi.org/10.1002/jimd.70049