ACCUMULATION OF G(M2) GANGLIOSIDE IN NIEMANN-PICK DISEASE TYPE-C FIBROBLASTS

Niemann-Pick disease type C (NP-C) is an autosomal recessive neurovisc eral lipid storage disorder biochemically characterized by a defect in intracellular transport of low-density lipoprotein (LDL)-derived chol esterol from the lysosome to other cellular sites. We have found subst antial accumulation of G(M2) ganglioside in NP-C fibroblasts. The intr acellular distribution of G(M2) ganglioside was similar to that of cho lesterol detected by filipin staining, indicating that the accumulatio n of G(M2) ganglioside is mainly lysosomal. The incorporation of N-ace tyl-D-[H-3]mannosamine into gangliosides was also increased in NP-C fi broblasts, especially into the G(M2) and G(M3) fractions. A culture co ndition which eliminates cholesterol accumulation does not eliminate G (M2) accumulation. It is suggested that the accumulation of G(M2) gang lioside together with the accumulation of cholesterol is a unique abno rmality in NP-C fibroblasts and that the defect in NP-C may involve in tracellular transport of both cholesterol and G(M2) ganglioside.