IEMbase 0304: NPC2-related Niemann-Pick disease type C2
Scope
| Field | Value |
|---|---|
| IEMbase ID | 304 |
| Nosology | 20.6.02.02 |
| Gene | NPC2 |
| External IDs | OMIM:607625; ORPHA:216981 |
| Generated mapping | MAPPED; Niemann_Pick_Disease_Type_C.yaml#NPC2 |
| Candidate DisMech targets | Niemann_Pick_Disease_Type_C.yaml#NPC2 |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents NPC2-related Niemann-Pick disease type C with the same core NPC neurovisceral signal as the NPC1 record: ataxia, behavioral disorder, clumsiness, foam cells, hepatosplenomegaly, language difficulties, sea-blue histiocytes, action dystonia, psychotic behavior, cognitive dysfunction, dysarthria, dystonia, gait disturbance, gelastic cataplexy, hemophagocytosis, cholestatic jaundice, oculomotor abnormalities, seizures, and vertical gaze palsy.
Biochemical rows are the same diagnostic cluster seen in NPC1: markedly increased plasma chitotriosidase, abnormal filipin testing, and increased plasma cholestane-3beta,5alpha,6beta-triol. Miglustat is the only treatment listed in the cached IEMbase record.
DisMech phenotype coverage
Niemann_Pick_Disease_Type_C.yaml explicitly distinguishes NPC2 from NPC1 in
has_subtypes, genetic, and subtype term mappings. The file models the
shared NPC phenotype spectrum, including vertical supranuclear gaze palsy,
ataxia, dysarthria, dysphagia, progressive mental deterioration, dystonia,
seizures, gelastic cataplexy, hepatosplenomegaly, neonatal cholestasis,
psychiatric manifestations, hepatomegaly, splenomegaly, gait disturbance,
jaundice, progressive neurologic deterioration, bone-marrow foam cells,
cognitive impairment, dysphonia, and feeding difficulties.
Biochemical coverage includes unesterified cholesterol accumulation, plasma 24(S)-hydroxycholesterol, sphingosine accumulation, low cholesterol esterification rate, and plasma phosphorylated-tau217. Treatment coverage is broader than IEMbase, with miglustat, intrathecal cyclodextrin, levacetylleucine, arimoclomol, supportive care, and genetic counseling.
Concordance and completeness
Judgement: correct high-confidence subtype mapping to
Niemann_Pick_Disease_Type_C.yaml#NPC2.
The local entry covers the important disease identity, gene split, shared NPC mechanism, and most clinical phenotypes. IEMbase is more granular for diagnostic lab rows and for some clinical rows that are only implicit or absent locally: plasma chitotriosidase, cholestane-triol, filipin test, language difficulties, hemophagocytosis, sea-blue histiocytes, and broad oculomotor abnormalities.
Treatment concordance is strong for miglustat. IEMbase does not list intrathecal cyclodextrin for NPC2, so the local HPbCD coverage should remain a general NPC treatment entry unless future curation adds subtype-specific treatment applicability.
Curation actions
- Keep the generated NPC2 subtype mapping.
- Add NPC diagnostic biomarker prompts for chitotriosidase and cholestane-triol if source evidence supports them.
- Review whether filipin testing should be modeled as an abnormal diagnostic assay rather than as a simple decreased/increased marker.
- Avoid inferring NPC2-specific HPbCD treatment from the IEMbase record.