Hepatosplenomegalic lipidosis: what unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase-1 exon 8 splice junction mutation

A 36-year-old woman was admitted for hepatosplenomegaly and anemia, Bone ma rrow cytology showed "sea-blue histiocytes", vacuolated macrophages and pla sma cells. As primary liver disease, malignancy or hematologic disorders we re excluded, and plasma chitotriosidase activity was increased 27-fold over control, the presence of a lysosomal storage disease was suspected. Bioche mical analysis of skin fibroblasts revealed normal glucocerebrosidase and s phingomyelinase activity, but lipid analysis showed a more than 15-fold acc umulation of cholesterol esters within the cells, The activity of lysosomal acid lipase (LAL) in fibroblast homogenates was decreased to 12% of contro l subjects, Mutational analysis of the patient's blood showed the homozygou s G-->A mutation at position -1 of the exon 8 splice donor site (E8SJM-alle le) known for adult cholesteryl ester storage disease (CESD); the polymorph ic background was that of the complex haplotype -6Thr, 2Gly, 894 G-->A. Bas ed on clinical, laboratory, cytological and and biochemical findings, CESD can clearly be separated from other more frequent inherited lysosomal stora ge diseases, e,g, atypical forms of Gaucher disease.