Crocker (1961) delineated 4 types of Niemann-Pick disease: the classic infantile form (type A; 257200), the visceral form (type B; 607616), the subacute or juvenile form (type C), and the Nova Scotian variant (type D; see 257220). Since ... Crocker (1961) delineated 4 types of Niemann-Pick disease: the classic infantile form (type A; 257200), the visceral form (type B; 607616), the subacute or juvenile form (type C), and the Nova Scotian variant (type D; see 257220). Since then, types E and F have also been described (see 607616).
Niemann-Pick type C (NPC) disease is an autosomal recessive lipid storage disorder that affects the viscera and central nervous system. The fatal damage in NPC disease is neurodegeneration starting from early life. NPC has a highly variable clinical ... Niemann-Pick type C (NPC) disease is an autosomal recessive lipid storage disorder that affects the viscera and central nervous system. The fatal damage in NPC disease is neurodegeneration starting from early life. NPC has a highly variable clinical phenotype (for a detailed phenotypic description, see NPC1; 257220). Vanier et al. (1996) reported 5 patients with NPC2. Three patients presented with a 'new' rare phenotype associated with severe pulmonary involvement leading to death within the first year of life. A fourth case in that group had typical neurovisceral disease with infantile neurologic onset and rapid course; the fifth case and her affected sister had a typical juvenile form of the disease. There was no common ethnic origin for the group 2 cases. Two were North African, whereas the other 3 were Italian, French, and German. Tissue lipid storage pattern, intralysosomal cholesterol storage, and abnormalities in cholesterol homeostasis were similar to NPC1. Millat et al. (2001) reported the first comprehensive study of 8 unrelated families with NPC2, originating from France, Algeria, Italy, Germany, the Czech Republic, and Turkey. These cases represented essentially all patients with NPC2 who had been reported, as well as those known to the authors. Seven families demonstrated severe and rapid disease course, with age at death being 6 months to 4 years. A remarkable feature was the pronounced lung involvement, leading, in 6 patients, to early death caused by respiratory failure. Two patients also developed a severe neurologic disease with onset during infancy. Klunemann et al. (2002) reported 2 sisters with a novel phenotypic variant of NPC2, confirmed by molecular analysis. Both sisters presented in their early forties with vertical supranuclear gaze paresis, dysarthria, and cognitive decline characterized by expressive aphasia, perseverative behavior, and impaired conceptualization and planning. The proband developed ataxia and athetoid movements, and her sister developed facial dyskinesias and bradykinesia. Cholesterol esterification of cultured fibroblasts from 1 patient was abnormally low at 26% of normal. Detailed histories revealed that both patients exhibited early cognitive symptoms in adolescence. Postmortem examination of the proband revealed frontal lobe atrophy and neuronal lysosomes with oligolamellar inclusions typical for NPC, but no visceromegaly.
In 2 patients with NPC2, Naureckiene et al. (2000) identified mutations in the HE1 (NPC2) gene (601015.0001-601015.0002).
In 6 unrelated patients with NPC2, Verot et al. (2007) identified 5 different mutations in the NPC2 gene (see, ... In 2 patients with NPC2, Naureckiene et al. (2000) identified mutations in the HE1 (NPC2) gene (601015.0001-601015.0002). In 6 unrelated patients with NPC2, Verot et al. (2007) identified 5 different mutations in the NPC2 gene (see, e.g., 601015.0008-601015.0010). The authors stated that a total of 15 disease-causing mutations had been identified in 22 unrelated families to date. E20X (601015.0001) was the most common mutation, accounting for 34% of mutant alleles.