IEMbase 0303: NPC1-related Niemann-Pick disease type C1
Scope
| Field | Value |
|---|---|
| IEMbase ID | 303 |
| Nosology | 20.6.01.01 |
| Gene | NPC1 |
| External IDs | OMIM:257220; ORPHA:216981 |
| Generated mapping | MAPPED; Niemann_Pick_Disease_Type_C.yaml#NPC1 |
| Candidate DisMech targets | Niemann_Pick_Disease_Type_C.yaml#NPC1 |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents NPC1-related Niemann-Pick disease type C as a neurovisceral lysosomal storage disorder. Characteristic rows include ataxia, behavioral disorder, clumsiness, foam cells, gait disturbance, hepatosplenomegaly, language difficulties, and sea-blue histiocytes. Additional clinical rows include action dystonia, psychotic behavior, cognitive dysfunction, dysarthria, dystonia, gelastic cataplexy, hemophagocytosis, cholestatic jaundice, hepatocellular carcinoma or hepatoblastoma, oculomotor abnormalities, seizures, and vertical gaze palsy.
The biochemical signal is diagnostic and storage-focused: markedly increased plasma chitotriosidase, an abnormal filipin test row, and increased plasma cholestane-3beta,5alpha,6beta-triol. Treatments in the cached record are miglustat and intrathecal 2-hydroxypropyl-beta-cyclodextrin.
DisMech phenotype coverage
Niemann_Pick_Disease_Type_C.yaml has explicit NPC1 and NPC2 subtypes, with
NPC1 as the correct generated target for this record. It covers the shared NPC
phenotype spectrum with vertical supranuclear gaze palsy, cerebellar 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.
Local biochemical coverage includes unesterified cholesterol accumulation, plasma 24(S)-hydroxycholesterol, sphingosine accumulation, low cholesterol esterification rate, and plasma phosphorylated-tau217. Treatments include miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, levacetylleucine, arimoclomol, supportive care, and genetic counseling.
Concordance and completeness
Judgement: correct high-confidence subtype mapping to
Niemann_Pick_Disease_Type_C.yaml#NPC1.
Concordance is high for gene identity, NPC1 subtype placement, recessive NPC biology, neurovisceral presentation, gaze palsy, ataxia, dystonia, seizures, gelastic cataplexy, hepatosplenomegaly, cholestatic jaundice, foam-cell pathology, cognitive/psychiatric involvement, and miglustat/HPbCD treatment context. DisMech is richer for mechanism and for newer or broader treatment coverage.
IEMbase adds review prompts for plasma chitotriosidase, plasma cholestane-3beta,5alpha,6beta-triol, explicit filipin-test directionality, language difficulty, hemophagocytosis, oculomotor abnormalities as a broader row than vertical gaze palsy, sea-blue histiocytes, and the hepatocellular carcinoma/hepatoblastoma row. The liver cancer row should be reviewed carefully before import because it may represent rare complication or source-spectrum noise rather than a core NPC1 phenotype.
Curation actions
- Keep the generated NPC1 subtype mapping.
- Consider adding chitotriosidase and cholestane-triol diagnostic biomarkers if source-backed.
- Review filipin-test directionality before modeling it, since the cached row is not directly phrased as cholesterol accumulation.
- Treat hemophagocytosis, sea-blue histiocytes, and liver tumor rows as review prompts rather than automatic phenotype imports.