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