Barth syndrome natural history in 502 individuals (>80% of known cases): • Highest mortality <5 yrs • Plateau 5–25 yrs (but disease burden ↑) • Cardiac causes dominate • Transplant & healthcare access improve survival A key dataset for timing intervention doi.org/10.1002/jimd...

57-year-old. Confusion + vomiting → rapid deterioration. Stroke? Infection? Something else? In this metabolic mystery, Dr Mark Wijnen (Erasmus MC) plays detective 🕵️‍♂️ The key clue is easy to miss and the diagnosis isn’t where most adult physicians look. soundcloud.com/user-1090061...

New global NPC clinical guidelines (2025) published. Updated diagnosis (biomarkers → genetics), evolving disease-modifying therapies, and a strong push for multidisciplinary care. A key reference for improving consistency — and reducing diagnostic delay. doi.org/10.1002/jimd...

Our Last SIMD Journal Club of the 2026/2027 academic year is this FRIDAY 5/1/26 at noon ET. Register here to join us- tinyurl.com/SIMDJournalC... #organicacidemia #inbornerrorsofmetabolism #inheritedmetabolicdisorders

Riboflavin in IMDs — helpful, but only in the right diseases. Systematic review (381 studies, 33 IMDs): ✔ Strong evidence: MADD3, RTD, ACAD9 ❓ Uncertain in many others ✖ Not effective in MADD1 ➡️ Think targeted therapy, not blanket use doi.org/10.1002/jimd...

Hydrops fetalis + corpus callosum agenesis + cardiac hypertrophy… when should we suspect mito disease antenatally? This case shows how rapid proteomics confirmed severe MRPS22-related mitochondrial disease after pregnancy loss, enabling diagnosis + reproductive counselling. doi.org/10.1002/jmd2...

Not all NPC1 variants behave the same. This new study shows that mutant trafficking phenotype directly correlates with cholesterol accumulation in NPC. p.I1061T = severe ER retention + highest cholesterol burden p.P1007A = near WT trafficking + mild phenotype doi.org/10.1002/jimd... #NPC

A young woman with years of severe abdo pain, neurological symptoms, anxiety, and repeated hospital visits Treated as FMF, the real answer only emerged when the right test was performed at the right time. Tanyel Zubarioglu presents a #MetabolicMystery Listen here: soundcloud.com/user-1090061...

PKU at-home monitoring moves forward: ✔️ 15 min PHE results ✔️ Good agreement with lab ⚠️ Positive bias (~85 μmol/L) ⚠️ Variability ↑ at home + with older batches Patients preferred it — but not ready to replace lab yet doi.org/10.1002/jimd...

Teriparatide in MPS IVB (n=2): ✔️ BMD ↑ / stabilised ⚠️ Both developed significant cardiac complications during treatment Signal only — not causality — but enough to warrant caution Also: height-adjusted BMD matters in short stature disorders doi.org/10.1002/jmd2...

Adults with UCDs report HRQoL similar to the general population in this UCDC cohort. But: → No difference between symptomatic vs “asymptomatic” → Cognitive differences don’t map to HRQoL → Signals suggest current tools may lack sensitivity 📄 doi.org/10.1002/jimd... #IMD #UCD #RareDisease

New JIMD Podcast episode: tyrosine hydroxylase deficiency. Mariya Sigatullina, Thomas Opladen and Ivana Badnjarevic discuss the first consensus guideline for diagnosis and treatment of THD, covering clinical spectrum, diagnosis, L-dopa use, and long-term care. open.spotify.com/episode/6msH...

4-year Phase III data for pegvaliase in adult PKU (Japan): • ~70% ↓ phenylalanine • Most achieve ≤360 µmol/L • Diet liberalisation common • AEs highest early, fall over time • No new safety concerns A useful long-term dataset. doi.org/10.1002/jmd2...

How do we measure neurodevelopment in paediatric LSDs? 📊 98 studies 🧠 38 caregiver-reported tools ⚖️ Heavy reliance on general measures ⬇️ Less consistent capture of cognition + communication 👉 Outcome selection is variable — and matters. doi.org/10.1002/jimd...

New JIMD Shortcast: Sophie Manoy discusses antenatal and neonatal management in carbonic anhydrase VA deficiency. After an older sibling presented critically on day 4 of life, 2 brothers were diagnosed antenatally and managed proactively without decompensation. open.spotify.com/episode/5sVz...

GSD IV isn’t just a paediatric disease. This study estimates: • 1 in 243 carriers • ~34,800 affected globally 👉 A single GBE1-related spectrum → early-onset ↔ adult APBD Likely underdiagnosed. 📄 onlinelibrary.wiley.com/doi/10.1002/... #RareDisease #Genetics

CSF diagnostics, simplified. A multimodal LC–MS/MS panel enables: • Broad metabolite coverage • Less CSF (250 μL) • Faster analysis (~65 min) Now implemented in routine diagnostics. 📄 doi.org/10.1002/jimd... #RareDisease #Metabolomics #Neurology

Real-world pegzilarginase data in arginase 1 deficiency (n=16): • ↓ plasma arginine by 3 months • Most <200 μmol/L • ↑ dietary protein intake with maintained control • No new safety signals Findings align with trial data. doi.org/10.1002/jmd2...

Why do outcomes vary so much in classic galactosaemia? This study shows: 🧬 Strong heritability of long-term complications ⚠️ GALT genotype explains <8% 🌍 Socioeconomic factors not associated 👉 Suggests genetic modifiers beyond GALT Important step toward personalised prognosis. doi.org/10.1002/jimd...

8 years That’s the average delay to diagnosing mitochondrial disease But many patients already had the right features documented years earlier Seizures. Hypotonia. Developmental delay. Stroke. The clue may already be in the notes 🎧 Shortcast with Dr Rory Tinker open.spotify.com/episode/6c2Z...

Can mRNA deliver what liver IMDs need? In our latest Podcast, we discuss mRNA therapy for liver inherited metabolic diseases including protein replacement, liver targeting with LNPs, and the appeal of flexible repeat dosing. open.spotify.com/episode/6umZ... #mRNA #genetherapy #raredisease

Do organoids need to look like organs to model disease? A new JIMD review argues that function may matter more than anatomy when studying inherited metabolic diseases. Focus on the pathway - not the organ. 🔗 doi.org/10.1002/jimd... #IMD #Organoids #RareDiseaseResearch

Check out our new JIMD Shortcast with Dr Aaron B. Bowen on the RHADS EEG pattern in succinate dehydrogenase deficiency and what it means for epilepsy evaluation in mitochondrial disease. #IMD #EEG #Epilepsy open.spotify.com/episode/2l5R...

A new MS/MS method for quantitative succinylacetone measurement improves sensitivity and specificity for diagnosing/monitoring tyrosinemia t1. ✔ Improved analytical specificity ✔ Useful for NBS follow-up and NTBC monitoring onlinelibrary.wiley.com/doi/10.1002/... #IMD #Tyrosinemia #RareDisease

TFP deficiency isn’t just an energy problem. New work suggests a role in cardiolipin remodeling, opening the door to elamipretide as add-on therapy. Prof Eduardo Vieira Neto discusses mice, fibroblasts, and the hunt for biomarkers to find responders. open.spotify.com/episode/0Hv9...

Antenatal diagnosis → planned neonatal care → avoided metabolic decompensation. This JIMD Reports case series shows how expectant management in siblings with carbonic anhydrase VA deficiency can change early outcomes in an ultra-rare IMD. 🔗 onlinelibrary.wiley.com/doi/10.1002/... #RareDisease #IMD

Ahead of #RareDiseaseDay (28 Feb), an important reminder: rare diseases can have rare presentations. Lynch et al. report adult-diagnosed GSD1b in siblings with prolonged fasting tolerance and minimal neutropenia doi.org/10.1002/jmd2... #RareDisease #GSD1b #IMD #GenomicMedicine

A sobering case of treatable molybdenum cofactor deficiency—diagnosed within hours, yet with rapid, unexpected decline before therapy could begin. In this Shortcast, Dr Molly Crenshaw reflects on urgency, optimism, and why early biochemical testing still matters open.spotify.com/episode/1p3w...

New in JIMD Reports: Open-label phase 2/3 substudy of intrathecal idursulfase-IT in children <3 years with neuronopathic MPS II. Reports long-term follow-up with generally stable cognitive assessments and reduced CSF GAG levels in a small cohort. 🔗 doi.org/10.1002/jmd2... #MPSII #HunterSyndrome# IMD

New in JIMD Reports: clinical and genetic insights into MSUD from Palestine, including neurodevelopmental outcomes after liver transplantation. A valuable real-world perspective from a resource-limited setting. 🔗 doi.org/10.1002/jmd2... #MSUD #RareDisease #IMD #LiverTransplant

Reducing the diagnostic odyssey in IMDs 🧠 Expert-designed fact sheets + AI/NLP validation using real hospital data show real promise for earlier diagnosis and referral. Open access in J Inherit Metab Dis 👉 doi.org/10.1002/jimd... #RareDisease #IMD #AIinMedicine #JIMD

Can newborn screening predict severity in VLCADD? Neonatal C18:2-carnitine (linoleylcarnitine) identifies infants at risk of severe disease immediately after NBS helping tailor treatment and monitoring from day one. 🔗 doi.org/10.1002/jimd...

Pregnancy outcomes in Gaucher disease: real-world data from the ICGG Registry. 110 imiglucerase-treated pregnancies → 88.5% live births, no stillbirths, miscarriage risk similar to the general population. 🔗 doi.org/10.1002/jimd...

Do adults with early-treated #PKU show altered brain ageing? MRI-based brain age modelling reveals a higher insular brain age gap (~6 years) despite early treatment — pointing to region-specific vulnerability rather than global ageing. 🔗 doi.org/10.1002/jimd... @emmavardy2.bsky.social

A powerful JIMD study reports a cluster of severe arginase-1 deficiency in children from Mayotte & the Comoros, linked to a founder effect. Early diagnosis = normal outcomes; delayed diagnosis = high morbidity & mortality. 🔗 doi.org/10.1002/jimd...

VUS ≠ surveillance. In The Grey Zone Project, Lund et al. propose LPC-based risk stratification for ABCD1 variants detected via newborn screening. Biochemistry — not variant label — determines monitoring intensity. Read: doi.org/10.1002/jimd... #ALD #NewbornScreening #RareDisease #JIMD

Women with Anderson–Fabry disease are still being missed. This meta-analysis shows genetic testing detects ~4× more cases than enzymatic tests in high-risk women — especially after stroke. Normal enzymes ≠ no Fabry. doi.org/10.1002/jimd... #FabryDisease #RareDisease

Largest natural-history study of arginase-1 deficiency to date (n=48). International trial data show universal motor impairment, frequent cognitive & speech deficits, reduced quality of life — and delayed diagnosis. 🔗 doi.org/10.1002/jimd...

New JIMD Reports case: severe hyperglycaemia and lactic acidosis in propionic acidemia, without hyperammonaemia. A clear look at how secondary mitochondrial dysfunction can shape acute management decisions in PA crises. doi.org/10.1002/jmd2...

RHADS is often taught as POLG-specific but it may not be. This case series describes RHADS and RHADS-like EEG patterns in SDHA deficiency, broadening the epilepsy phenotype of mitochondrial disease. Worth reading if you see refractory epilepsy + “POLG-like” EEGs. doi.org/10.1002/jmd2...

Primary mitochondrial disease supplement prescribing is 95%+ common, but globally non-uniform. No universal cocktail. Age & phenotype shape practice. Big Atlantic differences. Real risks of harm. Listen now: open.spotify.com/episode/2wdU...

Access to IMD therapies is becoming one of the defining equity challenges in rare disease. Cabello & Salinas examine why lifesaving IMD drugs remain out of reach in much of Latin America and what ethical, regulatory, and policy changes are needed to close the gap. 📄 doi.org/10.1002/jimd...

New case report in JIMD Reports: A novel PCK1 variant causing cytosolic PEPCK deficiency in two siblings, with dramatically different phenotypes, including reversible acute liver failure. Hyperglutaminemia + normal ammonia = key diagnostic clue. doi.org/10.1002/jmd2... #RareDisease #IMD #PCK1

🧠 New in JIMD: NKH is not just “high glycine”. This mouse model shows disrupted one-carbon folate metabolism, serine deficiency, and downstream lipid/myelination effects, pointing to new therapeutic targets beyond glycine lowering. 🔗 doi.org/10.1002/jimd... #NKH #IMD #Metabolism

Dr Herodes Guzman talks through a striking GSDIa case series where lactic acidosis persisted despite hypoglycaemia correction—prompting fresh thinking about mitochondrial involvement in metabolic crisis. Listen now: open.spotify.com/episode/2gRr... #GSDIa #IMD #RareDisease #MetabolicMedicine

📊 Brazilian MPS I patients show diverse pathogenic variants, including novel changes with implications for genotype–phenotype correlation. A must-read for clinicians & researchers in metabolic disease. 🔗 doi.org/10.1002/jimd... #IMD #Genomics #Pediatrics

In a multicentre cohort of 202 patients, Kristensen et al. show: • >50% develop liver disease • Highest risk in early-onset POLG • Infection-associated onset and polymerase-domain variants increase risk • Liver involvement strongly predicts poor survival doi.org/10.1002/jimd... #POLG #Mitodisease

Earlier ERT = better hearts 🫀 In infantile-onset Pompe disease, starting ERT ≤1 month leads to faster LVMI normalisation and improved cardiac remodelling. Another strong case for newborn screening and rapid treatment. 🔗 doi.org/10.1002/jmd2... #PompeDisease #IMD #NewbornScreening

Why does mitochondrial disease still take ~8 years to diagnose? This study shows most delay happens before suspicion, despite early seizures, hypotonia & stroke being documented years earlier. Recognition — not testing — is the bottleneck. doi.org/10.1002/jmd2...