Niemann-Pick disease type C. Pathological, histochemical, ultrastructural and biochemical studies.

Two sisters with Niemann-Pick Disease Type C suffered from a progressive CNS degenerative disease which ended with death at 8 and 7 years. Light microscopic and histochemical studies revealed storage of lipid (principally sphingomyelin) in the viscera and in the central nervous system (predominantly ganglioside). Complex lipid cytosomes containing stacked membranes, concentric laminated bodies with central dense cores and pleomorphic profiles were seen. Biochemical analysis showed an elevation of sphingomyelin in liver and spleen with normal total sphingomyelinase levels. However, by isoelectric focusing, there was a marked reduction of sphingomyelinase activity in the range of pI 4.6--5.2, whereas normal amounts of more acidic components were found. These data are compatible with autosomal recessive inheritance of a sphingomyelin lipidosis associated with deficiency of isoelectric forms of sphingomyelinase.