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

• Published in: Journal of hepatology Vol. 31; no. 4; pp. 741 - 746
• Main Authors: Dahl, Stephan vom, Harzer, Klaus, Rolfs, Arndt, Albrecht, Bettina, Niederau, Claus, Vogt, Christoph, Weely, Sonja van, Aerts, Johannes, Müller, Gerd, Häussinger, Dieter
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.10.1999
• Subjects: Adult; Anemia - complications; Biological and medical sciences; Cholesterol Ester Storage Disease - blood; Cholesterol Ester Storage Disease - complications; Cholesterol Ester Storage Disease - diagnosis; Diagnosis, Differential; DNA, Recombinant; Errors of metabolism; Exons; Female; Gaucher Disease - diagnosis; Hepatomegaly - complications; Hepatomegaly - diagnosis; Hexosaminidases - blood; Homozygote; Humans; Isoenzymes - genetics; Lipase - genetics; Lipidoses - complications; Lipidoses - diagnosis; Lipids (lysosomal enzyme disorders, storage diseases); Lipodystrophy - complications; Lipodystrophy - diagnosis; Lysosomes - enzymology; Medical sciences; Mesentery; Metabolic diseases; Mutation; Splenomegaly - complications; Splenomegaly - diagnosis; Human; Nervous system diseases; Ester polymer; Metabolic diseases; Sphingolipidosis; Enzymopathy; Cholesterol; Cerebral disorder; Genetic disease; Case study; Storage; Central nervous system disease; Female; Lipoidosis
• ISSN: 0168-8278
• DOI: 10.1016/S0168-8278(99)80356-0

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