Increase in Sterol Synthesis and Decrease in Cholesterol Efflux in Niemann-Pick Disease Type C Fibroblasts

Abstract

Niemann-Pick disease is an inborn error of metabolism characterized by a deficiency in sphingomyelinase activity and sphingomyelin storage in the A and B types. In the C type (NPC), cholesterol is often accumulated to a greater extent than sphingomyelin, and the primary defect is, at the present time, unknown. In previous studies, we pointed out close relationships between sphingomyelin and cholesterol metabolisms in human fibroblasts ^1,2 and we demonstrated that NPC fibroblasts are able to degrade exogenous sphingomyelin³. We also suggested that in NPC disease, the primary defect could concern cholesterol rather than sphingomyelin metabolism². Recently, a deficiency in cholesterol esterification has been described in NPC cells by Pentchev et al.^4,5. In the present study, we investigated different aspects of cholesterol metabolism in 3 NPC patients fibroblasts: sterol synthesis, esterification and efflux.