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IEMbase 0587: VPS11-related hypomyelinating leukodystrophy type 12

Scope

Field Value
IEMbase ID 587
Nosology 19.4.02.01
Gene VPS11
External IDs OMIM:616683; ORPHA:466934
Generated mapping UNMAPPED; best candidate Hypomyelinating_Leukodystrophy_7.yaml
Candidate DisMech targets None exact
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents VPS11-related hypomyelinating leukodystrophy type 12 / HLD12. The record is autosomal recessive, classified under disorders of lysosome-related organelle biogenesis, has unknown treatability, and has no treatment rows.

Biochemical rows include increased urinary monohexosylceramides, sulfatide, and tetrahexosylceramides. Clinical rows include blindness, hearing loss, hypotonia, spasticity, cerebral hypomyelination, cerebellar white-matter MRI abnormalities, thin corpus callosum, and temperature instability.

DisMech phenotype coverage

Hypomyelinating_Leukodystrophy_7.yaml is a phenotype-class false-positive candidate. It models POLR3A/POLR3B-related leukodystrophy / 4H syndrome through RNA polymerase III transcriptional dysfunction, not VPS11, HOPS/endolysosomal trafficking, lysosome-related organelle biogenesis, or urinary glycosphingolipid/sulfatide abnormalities.

The local knowledge base contains other hypomyelinating leukodystrophy entries, but no exact VPS11/HLD12 target was identified.

Concordance and completeness

Judgement: true local gap; reject HLD7 as an exact target.

IEMbase supplies a distinct VPS11 mechanism and biomarker profile that should remain separate from POLR3-related leukodystrophy. The overlapping hypomyelination, spasticity, and motor features explain the generated match but are not sufficient for disease identity.

Curation actions

  • Create or identify an exact VPS11/HLD12 target before import.
  • Reject Hypomyelinating_Leukodystrophy_7.yaml as an exact mapping.
  • Preserve the urinary glycosphingolipid/sulfatide, cerebral hypomyelination, cerebellar white-matter, thin corpus callosum, blindness, hearing-loss, hypotonia/spasticity, and temperature-instability prompts.