WOLMAN'S DISEASE: THREE NEW PATIENTS WITH A RECENTLY DESCRIBED LIPIDOSIS

Abstract

Three patients are presented, the first ones of American origin, with a newly identified constitutional lipidosis previously described by Wolman from Israel. The clinical picture as seen to date shows poor weight gain, vomiting and diarrhea, increasing hepatosplenomegaly with abdominal protuberance, and death in nutritional failure by 2-4 months of age. One of the patients in this report had a similarly involved sibling; present data suggest recessive genetic transmission. Foam cells are found in the bone marrow, and vacuolated lymphocytes in the peripheral blood, each entirely similar to those seen in Niemann-Pick disease. Serum lipids are normal, and signs of adrenocortical insufficiency are moderate. An apparently pathognomic radiologic sign is the presence of greatly enlarged adrenal glands, easily visible by virtue of diffuse punctate calcific deposits, with normal shape of the gland preserved. Pathologic studies show disseminated foam cells, laden with cholesterol and neutral fat, most notable in the liver, spleen, lymph nodes, marrow, thymus, and small intestinal mucosa. In addition, neutral fat deposits are found in connective tissue cells, vascular endothelium, bile ducts, hepatic parenchymal cells, and adrenal cortical cells. The adrenal enlargement is produced by increase in the adrenal cortex, with secondary, possibly ischemic, necrosis and calcification. Direct analysis of unfixed tissue has shown that the cholesterol level of the liver is increased 15-20-fold, and of the spleen 4-5 times normal, with apparent major increase in triglycerides as well. Nervous system changes are milder. The accumulated sterol has been demonstrated to be genuine cholesterol in the tissues studied so that the mechanism of the disease does not appear to rest with disturbed biosynthesis of cholesterol.