ABSTRACT
Niemann-Pick type C was first described in the review by Crocker and Farber [1] of their 18 patients with Niemann-Pick disease; the classic features of paralysis of upward gaze, ataxia, dystonia, spasticity and seizures were clearly described in one of the patients, all of whom had the characteristic foam cells and storage of sphingomyelin. They classified Niemann-Pick into types A and B (Chapter 95), C and D, which is now known to be a variant of C, described in a French-Acadian isolate in Nova Scotia [2]. When the defect in sphingomyelinase was found in types A and B by Brady and his colleagues [3], it became evident that this enzyme was normal in type C [4]. Pentchev and colleagues [5,6] discovered defective esterification of exogenous cholesterol in the mutant BALB/c mouse. This group then showed that the same faulty regulation of cholesterol processing and storage was present in cultured fibroblasts from patients with Niemann-Pick type C disease [7]. The study of complementation in somatic cell hybrids indicated that type D was allelic with type C on one gene, and clearly separate from types A and B [8].
