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Niemann-Pick disease type C
Subacute or juvenile form.
Epidemiology:
- rare
- prevalence: 1 case per 100,000 live births [1]
- may appear early in life or be delayed into the teen years
Pathology:
- abnormal endosomal-lysosomal trafficking
- cholesterol accumulation in lysosomes
- sphingomyelinase deficiency not demonstrated
Genetics:
- mutations in NPC1 (95%) or NPC2 gene (5%)
Clinical manifestations:
- disease onset from antenatal life to maturity
- life expectancy varies markedly with age of onset [1]
- hepatosplenomegaly (moderate)
- brain damage may be extensive
- inability to look up & down
- cataplexy
- epilepsy, seizures
- ataxia
- dystonia
- dysphagia
- dysarthria
- loss of vision
- hearing loss
- no peripheral neuropathy
Laboratory:
- NPC1 gene mutation
Special laboratory:
- swallowing assessment
Radiology:
- brain MRI normal or only atrophy
Differential diagnosis:
- Wilson disease
- cerebrotendinous xanthomatosis
- GM1 gangliosidosis or GM2 gangliosidosis
- Friedreich ataxia
Management:
- low-cholesterol diet often recommended, but benefit limited
- prognosis is variable; some patients live into adulthood
- miglustat for symptomatic patients with life expectancy of > 1 year [1]
- 2 new therapies FDA-approved Sept. 2024
- arimoclomol (Miplyffa) in combination with miglustat
- levacetylleucine (Aqneursa)
Related
cholesterol
sphingomyelin
Specific
Niemann-Pick disease type C1
Niemann-Pick disease type C2
General
Niemann-Pick disease
Properties
ACCUMULATION: sphingomyelin
cholesterol
References
- Geberhiwot T, Moro A, Dardis A, et al.
Consensus clinical management guidelines for Niemann-Pick
disease type C.
Orphanet J Rare Dis. 2018 Apr 6;13(1): 50.
PMID: 29625568 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889539/
- NINDS Niemann-Pick Disease Information Page
https://www.ninds.nih.gov/disorders/all-disorders/niemann-pick-disease-information-page