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 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.
vom Dahl
S
S
Division of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Düsseldorf, Germany.
Harzer
K
K
Rolfs
A
A
Albrecht
B
B
Niederau
C
C
Vogt
C
C
van Weely
S
S
Aerts
J
J
Müller
G
G
Häussinger
D
D
D000328:Adult; D000740:Anemia / Q000150:complications; D015217:Cholesterol Ester Storage Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis; D004274:DNA, Recombinant; D003937:Diagnosis, Differential; D005091:Exons; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis; D006529:Hepatomegaly / Q000150:complications* / Q000175:diagnosis*; D006596:Hexosaminidases / Q000097:blood; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008064:Lipidoses / Q000150:complications* / Q000175:diagnosis*; D008060:Lipodystrophy / Q000150:complications / Q000175:diagnosis; D008247:Lysosomes / Q000201:enzymology; D008643:Mesentery; D009154:Mutation; D013163:Splenomegaly / Q000150:complications* / Q000175:diagnosis*
D004274:DNA, Recombinant; D007527:Isoenzymes; D008049:Lipase; D006596:Hexosaminidases; C086400:chitotriosidase