Accumulation of G(M2) ganglioside in Niemann-Pick disease type C fibroblasts

Niemann-Pick disease type C (NP-C) is an autosomal recessive neurovisceral lipid storage disorder biochemically characterized by a defect in intracellular transport of low-density lipoprotein (LDL)-derived cholesterol from the lysosome to other cellular sites. We have found substantial accumulation of G(M2) ganglioside in NP-C fibroblasts. The intracellular distribution of G(M2) ganglioside was similar to that of cholesterol detected by filipin staining, indicating that the accumulation of G(M2) ganglioside is mainly lysosomal. The incorporation of N-acetyl-D-[H-3]mannosamine into gangliosides was also increased in NP-C fibroblasts, especially into the G(M2) and G(M3) fractions. A culture condition which eliminates cholesterol accumulation does not eliminate G(M2) accumulation. It is suggested that the accumulation of G(M2) ganglioside together with the accumulation of cholesterol is a unique abnormality in NP-C fibroblasts and that the defect in NP-C may involve intracellular transport of both cholesterol and G(M2) ganglioside.