Abstract
Two sisters are described with demonstrable splenomegaly already from infancy and,
after the age of 2—4 years, signs of slowly progressive encephalopathy, vacuolated
lymphocytes in the peripheral blood, and peculiar foam cells in the bone marrow aspirates.
They died at 7Ÿ and 6œ years. Widely spread in the brain, the nerve cell bodies were
found to show extensive ballooning. It was most striking in the brain stem and spinal
cord, while cerebellar structures were remarkably well preserved. The cytoplasm of
the ballooned nerve cells was filled with finely granular storage material stainable
as a readily soluble glycolipid. The spleen, liver and intestinal wall contained numerous
foamy PAS-positive macrophages. Chemical assays showed a ten-fold increase of lactosylceramide
and a modest one of minor gangliosides of brain cortex. No accumulation of sphingomyelin
could be revealed, and the sphingomyelinase activity was found to be normal. The ganglioside
GM1 β-galactosidase activity of leucocytes was reduced to 20–25% of normal, which indicated
a disturbance of the glycosaminoglycan metabolism. The tissue content of glycosaminoglycans
was, however, normal, but an accumulation of lactose was demonstrated in the spleen.
It is postulated that the primary enzymic defect is a disturbance of a lysosomal β-galactosidase
with a substrate specificity for lactose and other oligosaccharides with a terminal
β-galactosidic linkage.
Keyword
Niemann-Pick disease - neurovisceral storage disorder - lactosylceramide - lactose - GM1 -β-galactosidase deficiency
