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IEMbase 0064: HSD17B10-related HSD10 mitochondrial disease

Scope

Field Value
IEMbase ID 64
Nosology 10.1.15.01
Gene HSD17B10
External IDs OMIM:300438
Generated mapping UNMAPPED; best fuzzy candidate HSD10_Mitochondrial_Disease.yaml
Candidate DisMech targets HSD10_Mitochondrial_Disease.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as X-linked HSD17B10-related 17-beta-hydroxysteroid dehydrogenase type 10 deficiency, also called 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency or HSD10. Treatability is marked yes, but no specific treatment rows are present in the cached record.

The biochemical signal includes normal-high C5-OH 2-methyl-3-hydroxybutyrylcarnitine, normal-high C5:1 tiglylcarnitine, low fibroblast 17-beta-HSD10 activity, high urinary 2-methyl-3-hydroxybutyric acid, high urinary tiglylglycine, low-normal glucose, and normal-high CSF or plasma lactate.

The characteristic clinical signal includes cardiomyopathy, dystonia, lactic acidosis, psychomotor delay, psychomotor regression, and seizures. Additional features include basal ganglia lesions, white-matter brain atrophy, choreoathetosis, dysarthria, frontotemporal atrophy, sensorineural hearing loss, hypoglycemia, ketoacidosis, metabolic acidosis, male predominance, movement disorder, periventricular white-matter changes, rigidity, spasticity, and decreased vision.

DisMech phenotype coverage

The generated UNMAPPED status is a false negative despite the low fuzzy score. HSD10_Mitochondrial_Disease.yaml is the correct local target. DisMech models HSD10 mitochondrial disease as an X-linked neurodegenerative disorder caused by HSD17B10 variants affecting the multifunctional mitochondrial HSD10/MHBD protein. It explicitly covers the dual role in isoleucine/neurosteroid metabolism and mitochondrial RNase P/tRNA processing, with mitochondrial respiratory-chain dysfunction and energy failure as the central disease mechanism.

DisMech covers infantile, neonatal, juvenile, and atypical/asymptomatic forms, developmental regression, seizures, choreoathetosis, hypotonia, cardiomyopathy, retinopathy, visual loss, 2-methyl-3-hydroxybutyric aciduria, lactic acidosis, X-linked inheritance with variable female manifestations, supportive care, and historical isoleucine-restricted diet as a non-curative approach.

Concordance and completeness

Judgement: false-negative generated mapping; high manual concordance with HSD10_Mitochondrial_Disease.yaml.

IEMbase adds granular lab and imaging features that are not all explicit in the DisMech summary: C5-OH 2-methyl-3-hydroxybutyrylcarnitine, C5:1 tiglylcarnitine, fibroblast enzyme activity, urinary tiglylglycine, CSF lactate, basal ganglia lesions, frontotemporal atrophy, sensorineural hearing loss, ketoacidosis, periventricular white-matter changes, rigidity, spasticity, and dysarthria. DisMech is stronger for current mechanism, especially mitochondrial RNA processing rather than a purely isoleucine-metabolism framing.

Curation actions

  • Update mapping logic so HSD17B10/HSD10 resolves to HSD10_Mitochondrial_Disease.yaml.
  • Treat IEMbase's "treatability yes" cautiously because no treatment rows are present and DisMech records no effective disease-modifying therapy.
  • Consider IEMbase-specific acylcarnitine and neuroimaging details as future diagnostic/phenotype enrichments.