Reinvestigation of the pathogenesis of familial xanthomatosis through conjoint cytochemical, ultrastructural, and biochemical studies

Abstract

Autopsy tissues of a patient with Wolman's disease were examined biochemically, cytochemically, and with an electron microscope. In all tissues except brain, lysosomes of the cells of the reticuloendothelial system were filled with droplets of triglycerides and with cholesterol ester crystals. The parenchymal cells of adrenals and liver contained these compounds within large vacuoles which did not appear to be lysosomal in origin but which derived from, or were part of, the smooth and the rough endoplasmic reticulum cisternae. Most lysosomes of parenchymal cells were morphologically normal. Their acid β-glycerophosphatase activity was normal in liver hepatocytes and enhanced in parenchymal cells of the adrenals. These data suggest that an excessive synthesis of lipids rather than a deficiency of lysosomal “acid lipase” is responsible for the disease. However, a partial deficiency in acid lipase was found biochemically in the tissues examined. The apparent contradiction between biochemical and morphological data is discussed by the authors.