Prenatal diagnosis and fetal pathology of Niemann-Pick disease.

Prenatal diagnosis was successfully accomplished by determining sphingomyelinase activity in the cultured amniotic fluid cells in a case of high risk pregnancy for Niemann-Pick disease (NPD), type A. No detectable activity of sphingomyelinase was found in the cultured amniotic fluid cells obtained at the 17th week of gestation. Patient's pregnancy was terminated and the aborted fetus was proved to be affected with NPD. The liver, brain and skin fibroblasts from the aborted fetus revealed a markedly diminished activity of sphingomyelinase. Sphingomyelin content in the liver of the affected fetus was found to be increased approximately sevenfold as compared with that in a control fetus liver. On the other hand, there was no increase of sphingomyelin in the brain from the affected fetus. No significant increase in cholesterol content was found in the liver and brain from the affected fetus. Electron-microscopic findings revealed membranous cytoplasmic bodies and electron dense material with vacuoles in cytoplasm of the liver cell and a number of Zebra body-like inclusions in the cerebral vessel wall. Biochemical and histological findings of the NPD fetus indicate that there is the progress of the disorder already in the midtrimester of gestation.