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

Metabolic mysteries: Incidental adrenal calcifications in a neonate

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

Footprints of IMD: Movement Disorders... with Dakota Peacock and Darius Ebrahimi-Fakhari

Shortcast: Clinical and Developmental Outcomes after 50 Years of Galactosaemia NBS in Ireland

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

Adenosine Kinase

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

Penetrance, expressivity, and outcomes in classic galactosemia

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.

IMD Research Round-Up: Untargeted metabolomics

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

Pharmacological chaperones in OTC deficiency

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

Geriatric IMD: Diagnosing inherited metabolic disorders in older adults

Here’s a polished podcast blurb suitable for LinkedIn, BlueSky, or Apple Podcasts listings — written in the JIMD Podcast tone and style:

⸻
It’s one of the most talked-about breakthroughs of 2025, a first-in-human demonstration of in vivo gene editing to treat an inherited metabolic disease.

In this episode, Kiran Musunuru and Rebecca Ahrens-Nicklas are joined by Julien Baruteau to unpack what this means for the field. They explore the science behind gene editing, the importance of ethical design, and the emotional weight of stopping therapy once enzyme function is restored.

The conversation bridges the NEJM landmark paper (Musunuru et al., 2025) and the accompanying JIMD editorial (Rahman & Baruteau, 2025), reflecting on what this moment tells us about the future of metabolic medicine and how ready we are for it.

First in Human Gene Editing for an Inherited Metabolic Disease
Shamima Rahman, Julien Baruteau
https://doi.org/10.1002/jimd.70056

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease
Kiran Musunuru, et al
https://www.nejm.org/doi/10.1056/NEJMoa2504747

First in human gene editing: a new era for IMD therapies

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

Metabolic mysteries: A 61-year-old with rhabdomyolysis and lifelong episodic fatigue

JIMD Podcasts is home to the Journal of Inherited Metabolic Disease podcast and the JIMD Shortcast. We're also proud to showcase Metabolic Mysteries and the new Footprints in IMD podcast.

New tracks tagged #inborn errors of metabolism