Niemann-Pick disease type C (NPC) is an autosomal recessive cholesterol processing disorder characterized by the accumulation of low density lipoprotein (LDL) cholesterol in lysosomes leading to progressive neurodegeneration¹.  It is estimated that NPC arises in 1 case per every 120,000 births² with an estimated prevalence of 1:150,000 in Western Europe³.  NPC can present in infants, children, and adults with a highly variable clinical phenotype.  Neonates can present with ascites and severe liver disease and/or respiratory failure from infiltration of the liver and the lungs.  Infants without liver or respiratory disease tend to present with developmental delay and hypotonia^2,4.  Patients with 'classic' childhood onset of the disease develop symptoms between 2 and 4 years of age, showing progressive neurodegeneration and hepatosplenomegaly which can lead to death during early childhood.  Neurologic abnormalities develop gradually and are initially manifested by ataxia, dystonia, grand mal seizures, vertical supranuclear gaze palsy, dementia and psychiatric manifestations^2,4.  Adult-onset forms, with insidious onset and slower progression, are more likely to present with dementia or psychiatric symptoms². 

The diagnosis of NPC is confirmed by biochemical testing and/or molecular genetic testing.  Biochemical testing can demonstrate impaired cholesterol esterification and positive filipin staining in cultured fibroblasts.  Molecular genetic testing of the NPC1 and NPC2 genes by sequence analysis detects disease-causing mutations in approximately 94% of NPC individuals with ~95% mutations observed in NPC1 and ~5% in NPC2^2,5.