Late-onset OTC can hide outside the exons. This series shows a promoter variant c.-106C>A causing major enzyme loss & severe hyperammonaemia - diagnosis only possible with regulatory sequencing. A real lesson in looking beyond coding DNA. doi.org/10.1002/jmd2...

BIMDG 2026 is open! Join us in Oxford for an engaging programme, new ideas, and the chance to reconnect with colleagues. Pre-meeting: 29 June Symposium: 30 June–1 July Leonardo Royal Hotel, Oxford Abstract deadline: 15 April, 10:00 👉 www.bimdgconference.co.uk #BIMDG2026

Natural history matters, especially in lysosomal disease. Using Gaucher disease as a model, this review shows how deep phenotyping, modern genomics, biomarkers like lyso-Gb1, and multi-state disease modelling can turn registries into precision care and drug development. doi.org/10.1002/jimd...

Late-stage Leigh syndrome shows just how vulnerable the heart is to mitochondrial stress. In Ndufs4 KO mice, near-complete complex I loss forces a shift toward complex II respiration, yet cardiac energy substrates are profoundly depleted. 🔗 doi.org/10.1002/jimd... #LeighSyndrome

New JIMD Shortcast Cell trafficking disorders can mimic mitochondrial, lysosomal, or CDG because the defect lies within the cell. Merve Yoldaş Çelik discusses a 14-patient case series and why a mechanism-based diagnostic approach matters. Listen: open.spotify.com/episode/448f... #ThinkMetabolic

New in JIMD Reports 🧬 In HT-1, succinylacetone suppression outperforms NTBC blood levels as a marker of metabolic control. δ-ALA & AFP remain key; DBS has limits for tyrosine monitoring. 🔗 doi.org/10.1002/jmd2...

Elamipretide strengthens mitochondrial function in TFP models, without shifting total cardiolipin levels. bTFP-deficient mice ran ~2× farther, showed higher FAO-ETC enzyme activity, more ETC supercomplexes, and lower ROS, with a genotype-dependent response in patient fibroblasts.

From Molecule to Meaning: GM1 biomarkers Fluid markers track substrate burden + axonal injury (LysoSLs, gangliosides, glycans, NfL, CHITO, AST). Quant MRI/MRS + differential tractography provide the missing spatial context when atlases fail. doi.org/10.1002/jimd...

Allogeneic HSCT does not correct Sialidosis (Mucolipidosis Type I) despite early diagnosis and full donor engraftment of non-carrier leucocytes. doi.org/10.1002/jimd...

Manganese is essential… until it isn’t. 🚨 Dystonia 🧠 T1-bright basal ganglia 🩸 Polycythaemia 💉 EDTA chelation 🧪 Search for better, oral chelators Karin Tuschl, Suvasini Sharma and John Spencer unpack transporter defects, diagnosis, and chelation open.spotify.com/episode/1Wc5... #RareDisease #IMD

GA1 phenotype expanded: peripheral neuropathy is frequent and mostly subclinical in high-excretors, correlating with age and extrastriatal MRI changes, independent of movement disorder or acute striatal injury. doi.org/10.1002/jimd...

HPP muscle fibres show major mitochondrial respiratory impairment in Akp2GW−/− mice. Efzimfotase alfa restored maximal respiration to WT levels and fully rescued spare respiratory capacity. doi.org/10.1002/jmd2... #RareDisease #HPP #Mitochondria #EnzymeReplacementTherapy #OpenAccess

🎙️ New JIMD Shortcast Leukodystrophy caused by biallelic HMBS variants behaves very differently from acute intermittent porphyria and does not respond to liver-directed therapies. 🎧 Listen now: open.spotify.com/episode/5qWM... #RareDisease #Leukodystrophy #Porphyria #MetabolicNeurology #IMD

Cell trafficking disorders are genetically diverse, clinically convergent, and still easy to miss. This series highlights lactate elevation and dicarboxylic aciduria as recurring signals of ER-mitochondrial stress, pushing us toward mechanism-based diagnosis. doi.org/10.1002/jmd2... #CTD #IMD

In GSDIa, lactic acidosis can persist even after glucose correction, potentially reflecting mitochondrial dysfunction and driving multiorgan failure. Important signals for future mitochondrial surveillance and adjunct therapies in crisis care. doi.org/10.1002/jmd2... #GSDIa #Mitochondria

CoQ10 (25 mg/kg/day) reversed acute LV dysfunction in a 12-year-old with cblB (MMA) within 72h the first report of cardiomyopathy reversal in MMA using CoQ10 Supports secondary mitochondrial dysfunction & functional cardiac CoQ10 deficiency as a key mechanism. doi.org/10.1002/jmd2...

🎧 JIMD Podcast 2025: 50 episodes, 120+ territories, one very niche fandom crossover Here’s to 2026 and the next 30,000 plays, and remember, just search for "JIMD Podcasts" wherever you like to listen. #raredisease #podcast #inheritedmetabolicdisease #inbornerrorsofmetabolism #sciencecommunication

New JIMD Podcast I speak with Jean-Marie Saudubray and Manuel Schiff about six decades of progress in inherited metabolic diseases from early chromatography to genomics and the changing identity of the field. A rare, fascinating look at our history. open.spotify.com/episode/5ve2...

Is human d-glycerate kinase cytosolic or mitochondrial? This study shows GLYCTK is exclusively mitochondrial, and that the proposed GLYCTK2 isoform is likely non-functional — correcting long-standing database assumptions. 🔗 doi.org/10.1002/jimd... #IMD #RareDisease #Mitochondria

Are lipid abnormalities in PPi deficiency syndromes part of the disease mechanism? This narrative review explores how disrupted PPi homeostasis intersects with lipid metabolism across PXE, GACI, ACDC, ankylosis and HGPS. doi.org/10.1002/jimd...

New JIMD Podcast 🎙️ Terry Derks, Alessandro Rossi, Sarah Grünert and Yunkoo Kang explore CGM in liver GSD – from global consensus around standards of care to a new deep-learning model predicting hypoglycaemia before it happens. A new step towards personalised care soundcloud.com/user-1090061...

How should we make fair decisions about expensive drugs for rare diseases? A new Review by Bashir Jiwani argues that no single ethical theory can solve EDRD decisions, so legitimacy must come from transparent, inclusive, deliberative processes. onlinelibrary.wiley.com/doi/10.1002/... #Bioethics

Leukodystrophy due to biallelic HMBS variants is a rare condition distinct from acute intermittent porphyria, characterised by progressive leukoencephalopathy, not neurovisceral attacks. Liver Tx and hepatically directed therapies are unlikely to be effective 👉 DOI: doi.org/10.1002/jmd2...

New in JIMD: shifting IEM nutrition from control → optimisation. Personalised natural protein + adequate energy, targeted AA supplementation, and a lifespan framework, supported by tech/microbiome/pharmacologic tools. DOI: doi.org/10.1002/jimd... #IMD #IEM #MetabolicNutrition #JIMD

New: the largest D-bifunctional protein deficiency cohort in nearly 20 years Neonatal encephalopathy remains typical, but adult survival is possible even in neonatal-onset cases And importantly: normal/mild VLCFAs don't rule out DBP-D. doi.org/10.1002/jimd... #DBPD #Peroxisomal #RareDisease #JIMD

Persistent autophagy activation contributes to renal fibrosis in GSD-Ia 🧬 New work from Cheol Lee, Kunal Pratap, Sudeep Gautam, Lisa Zhang, Hung Dar Chen, Yoke Peng Loh, Brian C. Mansfield & Janice Y. Chou (NIH) links the Cyclin G1/CDK5 axis to maladaptive kidney repair. 🔗 doi.org/10.1002/jimd...

Too much of a good thing? Are we giving our patients too much amino acid mixture in MMA & PA? New work reviews dietary practice in 71 patients. AAM use may worsen BCAA imbalance and is linked with poorer nutritional & clinical scores, despite improving total protein intake. doi.org/10.1002/jimd...

New review on untargeted metabolomics in IMDs: • Detects thousands of metabolites at once • Finds new biomarkers (PDE, HPII, GLUT1DS) • Supports variant interpretation • Reveals pathophysiology and guides therapy monitoring doi.org/10.1002/jimd...

2 maternal–fetal PKU pregnancies successfully managed. Notable finding: Phe tolerance rose >300% despite fetal PAH deficiency, suggesting regulators of Phe tolerance extend beyond fetal enzyme activity. doi.org/10.1002/jmd2...

New data from the Dutch ALD cohort show that over half of adult male ALD patients experience sexual dysfunction, yet most have normal testosterone. Neurological impairment from myelopathy was the strongest predictor. doi.org/10.1002/jimd...

New HOS data provides the largest analysis to date of female patients with MPS II. Just 1.1% of the registry, these patients show high multisystem burden, frequent surgeries, and 57% cognitive impairment. Useful insights for earlier diagnosis and timely ERT. doi.org/10.1002/jmd2...

🎧 New shortcast! Katie Sapp & Allyson Tyrrell walk us through the challenges of newborn screening for LSDs and why multitier testing is the way forward. Based on their latest JIMD Reports paper. open.spotify.com/episode/3cMh... #ThinkMetabolic #NewbornScreening #LSD #RareDisease #JIMDshortcast

New #JIMD guideline out now: 🧬 Tyrosine Hydroxylase Deficiency (THD) Led by the iNTD network, it sets out how to: Diagnose via CSF + genetics Treat with L-dopa/DCI Plan multidisciplinary care 📘 Consensus from 28 experts & patient reps. 👉 doi.org/10.1002/jimd... #THD #RareDisease #MetabolicMedicine

How late is too late to start CDCA in CTX? We put that question directly to Tanyel Zübarioğlu, lead author of the largest long-term CTX treatment study to date. The answer may change how you think about prognosis, access, and the real-world impact of CDCA therapy. soundcloud.com/user-1090061...

🧩 New in JIMD: a simple screening tool helps non-neurologists detect movement disorders in metabolic patients boosting sensitivity from 68% → 87%. Quick, structured, and now validated. Read open access 👉 doi.org/10.1002/jimd... #JIMD #MovementDisorders #RareDisease

🎧 The JIMD Podcast Research Round-Up is back! Silvia Radenkovic & Rodrigo Starosta welcome Hilary Vernon & Austin Larson for a deep dive into mitochondrial disease — biomarkers, omics, and new therapeutic frontiers. ➡️ Listen now: open.spotify.com/episode/0cUZ... #MitochondrialDisease #RareDisease

If you heard the line about “switching off genes to treat OTC deficiency” in the latest JIMD Podcast — this is the story behind it. Knocking down hepatic GLS2 reduced ammonia levels and mortality in a mouse UCD model. 🎧 Podcast: open.spotify.com/episode/6gv3... #JIMD #ThinkMetabolic

New in JIMD Reports: severe neurological presentation in siblings with COQ5-related primary CoQ10 deficiency — featuring recurrent strokes, optic atrophy, and functional validation in yeast. 🧬 Expanding the molecular and clinical spectrum of this ultra-rare disorder. 👉 doi.org/10.1002/jmd2...

New in #JIMD 🔬 “Removal of Toxic Metabolites, Chelation: Manganese Disorders” From Na₂CaEDTA to novel Mn-specific ligands, this review explores how chemistry can help tackle hypermanganesemia and manganism. 👉 doi.org/10.1002/jimd... #Manganese #Chelation #RareDisease #MetabolicMedicine

A baby with CPS1 deficiency, a world-first use of in vivo gene editing, and the emotional, ethical, and scientific questions that follow. In the latest Podcast, Kiran Musunuru, Rebecca Ahrens-Nicklas, and Julien Baruteau discuss. open.spotify.com/episode/3m2r...

A 61-year-old with rhabdomyolysis, prolonged QT, and recurrent fatigue… but what ties it all together? Dr Samuel Mackenzie joins Metabolic Mysteries to unravel a case that proves you’re never too old for a metabolic diagnosis. 🎧 New episode out now | on.soundcloud.com/l8QjmKo5JFvA...

New insights into kidney disease in #MMA & #PA 👇 Zeyer et al. identify TGF-β-driven fibrosis as a key mechanism and show that losartan can normalize ECM remodeling in patient-derived cells. A promising step toward antifibrotic therapy in organic acidurias. 🔗 doi.org/10.1002/jimd... #Losartan

A vital but underused part of IMD care New @ernmetabern.bsky.social survey across 23 countries finds most IMD centres have palliative care but few patients are referred. Early, integrated, family-centred palliative care should be part of the metabolic pathway. doi.org/10.1002/jimd...

Trial readiness starts long before a drug enters the clinic. New JIMD review from Opladen & colleagues (Heidelberg) shows how understanding the natural history of IMDs, through registries, RWD, PROMs & predictive models, underpins every successful rare disease trial. 🔗 doi.org/10.1002/jimd.70102

In this new episode, François Maillot and Ida Schwartz discuss their systematic review of IMDs diagnosed in adults over 65. The findings reveal decades-long diagnostic delays and remind us to Think Metabolic at any age. Spotify: open.spotify.com/episode/7qdL... Or wherever you get your podcasts.

🧬 National data from Japan: 91% hyperammonemia • 50% intellectual disability • LT helps but can’t cure • Early diagnosis is key. onlinelibrary.wiley.com/doi/10.1002/... #ThinkMetabolic #JIMD

New in JIMD: Epifani et al. identify a circulating miRNA signature for PMM2-CDG. 6 key miRNAs → AUC > 0.9 using machine learning; miR-122-5p emerges as a liver-linked marker reflecting neurological & endocrine pathways. 🧬 Toward blood-based biomarkers for CDG. 🔗 doi.org/10.1002/jimd...

New in JIMD Reports: First expanded-access treatment with govorestat (AT-007) in a child with PMM2-CDG: safe, well-tolerated, and linked to improved liver enzymes, coagulation factors, and developmental scores. 🔗 doi.org/10.1002/jmd2... #CDG #PMM2 #JIMDReports #RareDisease

🎧 New #ResearchRoundUp! With Rodrigo away, James Nurse joins Silvia Radenkovic to chat with Dr Judith Jans and Dr Devin Oglesbee about the promise and pitfalls of untargeted metabolomics in IMD diagnostics. 🎙️ Listen here: open.spotify.com/episode/6YbH... #JIMDPodcast #Metabolomics #ThinkMetabolic

From lifesaving to life-improving: liver transplantation is reshaping how we treat inherited metabolic diseases. This excellent review explores evolving indications, outcomes > 90%, and the precision-medicine future of metabolic transplant care. onlinelibrary.wiley.com/doi/10.1002/... #JIMD #IMD