Cholesterylester-Speicherkrankheit

Abstract

Hepatomegaly and a slight to moderate elevation of serum transaminases were detected in four children (three boys two of whom were siblings, and one girl) at the age of 4–6 years. The clinical course was followed up to 6 years during which time there were few or no other signs of disease. In liver biopsies which were taken repeatedly in some cases, the mainlight microscopical findings were: 1) fibrosis or developing micronodular cirrhoses; 2) hepatocellular vacuoles resembling those in ordinary fatty infiltration; 3) enlargement of Kupffer cells by smaller vacuoles and by PAS-positive granules; 4) foam cells lying in the connective tissue of the portal tracts; 5) massive storage of birefringent material, especially in hepatocytes, which was detected in frozen sections and gave a positive reaction for cholesterol by the Schultz method.Electron microscopical examination showed: 1) cytoplasmic inclusions in the hepatocytes containing material which in part seemed to solubilize during the preparation and tended to form crystals in one case after formalin fixation and storage at 4° C. Some other material was moderatly osmiophilic without detectable substructure. 2) these inclusions were limited by characteristic „membrane complex” of 13–14 nm thickness, consisting of a true vacuole membrane, a submembraneous “halo” which is characteristic for lysosomes, and a thin limiting layer which has also been described in Tangier disease where the inclusions contain cholesteryl esters, but are not limited by a membrane; 3) heterogeneous storage material in Kupffer cells which is partly changed to lipopigment; 4) membrane limited vacuoles containing partly dissolved, partly osmiophilic lipid in the epithelial cells of small bile ducts as well as in endothelial cells. The diagnosis cholesteryl ester storage disease was confirmed in one case by lipid analysis of a liver biopsy, and in the remaining three cases by fibroblast cultures which showed a significant reduction in acid esterase activity. Hepatomegaly and fibrosis may precede the lipid storage as detected by light microscopy in paraffin sections. Therefore, the liver damage in cholesteryl ester storage disease does not seem to be due to intralysosomal lipid storage per se, but rather to an as yet undefined secondary disturbance of hepatocellular metabolism.