Neurovisceral lipidosis compatible with Niemann-Pick disease type C: morphological and biochemical studies of a late infantile case and enzyme and lipid assays in a prenatal case of the same family

One postnatal and one prenatal case (same family) of a neurovisceral lipidosis compatible with a diagnosis of Niemann-Pick disease type C were studied. The postnatal case, aged 4 and 6/12 at death, was characterized morphologically (foamy cells in the bone marrow; storage histiocytes in rectal submucosa and extraneural viscera and ballooned neurons, the two types of cells containing pleomorphic and oligomenbranous inclusion bodies, respectively; central demyelination) as well as biochemically (elevated spleen and liver content of sphingomyelin, cholesterol, glucosyl ceramide and lysobisphosphatidic acid). Sphingomyelinase activity (SM) was not significantly lowered and showed no greatly abnormal electrofocused pattern of activity; its extractability from brain, liver and spleen was distinctly hindered, a finding interpreted as expression of a reduced bioavailability of the enzyme. — The prenatal case was diagnosed by low SM in amniotic fluid. Diminished SM was confirmed in cultured amniotic cells and in tissues of the aborted fetus which, additionally, showed an elevated sphingomyelin and cholesterol content in the liver. A prenatal diagnosis of Niemann-Pick disease type C was made for the first time. The phenotypical variation of the disease may reflect genetic heterogeneity and, there-fore, a prenatally lowered SM need not be a constant finding. — The apparent normalization of SM in the postnatal case was accompanied by a decrease of visceromegaly raising the question of a causal relationship between the two phenomena.