Niemann-Pick disease type C (NPC) was demonstrated in two successive pregnancies by strongly reduced activity of sphingomyelinase in amniotic fluid cells. By contrast, chorionic villi from the first pregnancy had shown normal sphingomyelinase activity. The prenatal diagnosis of NPC in the two fetuses was confirmed, after termination of the pregnancies, by (phospho)lipid analyses of the fetal livers, by the assay of sphingomyelinase in the fetal fibroblasts and by the demonstration of a defective esterification of exogenous cholesterol and of cholesterol accumulation by filipin staining. Retrospective analysis of cultured amniocytes for cholesterol esterification and filipin staining confirmed the feasibility of these methods for prenatal diagnosis. In a recent pregnancy in the same mother the three available methods were applied to amniotic fluid cells and an unaffected child was correctly predicted. Lipid analysis of liver tissue from the patient with NPC and the two fetuses showed a 3–5 times increased level of cholesterol, a 2–3 times increased level of sphingomyelin and a remarkable increase of bis (monoacylglyceryl) phosphate.

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Clinica Chimica Acta
Department of Clinical Genetics

de Winter, J. M., Janse, H., van Diggelen, O., Loss, F., Beemer, F., & Kleijer, W. (1992). Prenatal diagnosis of Niemann-Pick disease type C. Clinica Chimica Acta, 208(3), 173–181. doi:10.1016/0009-8981(92)90074-Z