Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms

Abstract

Phospholipid levels and enzyme activities were measured in brain and spleen samples from patients with the three major variants of Niemann-Pick disease. Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen from types A and B and group C Niemann-Pick disease, whereas only in type A Niemann-Pick brain was the sphingomyelin concentration increased. Sphingomyelinase activity was markedly deficient in type A Niemann-Pick brain and spleen but residual activity of approximately 12% of control was measured in type B Niemann-Pick brain. Normal or raised sphingomyelinase and beta-glucosidase activities were measured in group C Niemann-Pick brain and spleen. Significant (17% of control) residual beta-glucosidase activity was also measured in non-neuropathic Gaucher brain. Normal levels of neutral sphingomyelinase activity were measured in brain samples from the three variants of Niemann-Pick disease. Acid sphingomyelinase activity in group C Niemann-Pick brain appeared normal with respect to enzyme extraction, pH optimum (pH 5.0) and apparent Km (approximately 0.4 mmol/L). Isoelectric focusing of brain sphingomyelinase revealed a degree of heterogeneity with activity peaks between pI 4.5 and 6.5. No defect was observed in group C Niemann-Pick brain and, although attenuated, all peaks were present in type B Niemann-Pick brain.