Niemann-Pick Type C is distinct from Types A and B both in clinical features and biochemical mechanism. There is accumulation of unesterified cholesterol and other lipids. There are many variant phenotypes with the classic phenotype described here seen in only about half of the patients.
Inheritance: autosomal recessive
Genetic locus: NPC1 (on chromosome 18) or NPC2
|
Clinical Findings |
Infancy |
Juvenile |
Adolescent or Adult |
|
hepatospleno-megaly |
present |
usually absent |
usually absent |
|
muscle tone |
hypotonia |
dystonia, cataplexy |
|
|
motor function |
delayed development, clumsy |
impaired fine movements, dysarthria, dysphagia |
dysphagia, progressive deterioration, chairbound |
|
ataxia |
present |
present |
present |
|
seizures |
|
present |
present |
|
behavior |
|
problems in school |
psychosis |
|
intellectual ability |
|
impaired |
dementia |
|
vertical supra-nuclear gaze palsy (VSGP) |
may be present in late infancy |
present |
may be present |
|
other |
variable neonatal jaundice |
|
respiratory complications of aspiration |
Histologic findings:
(1) Clusters of foamy macrophages or sea blue histiocytes may be seen in bone marrow and liver biopsies in patients with hepatosplenomegaly, but may be absent.
(2) Polymorphous cytoplasmic bodies are characteristic inclusions seen in skin or conjunctival biopsies.
(3) Cytoplasmic ballooning and inclusions are present within neurons of the CNS.
Definitive diagnosis requires testing cultured fibroblasts following LDL uptake. Affected patients show:
(1) characteristic filipin-cholesterol staining of perinuclear vacuoles (filipin is a fluorescent probe that complexes with unesterified cholesterol)
(2) measurement of cholesterol esterification
Death in the classic form tends to occur in early adulthood
Specialty: Genetics
ICD-10: ,
