Case ReportHepatosplenomegalic 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
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Case Report
A 36-year-old female patient was admitted because of hepatosplenomegaly and anemia. At the age of 2 years, icterus and slightly raised brownish skin spots had developed and hepatomegaly was diagnosed. A lipid storage disease was suspected and a fat-restricted diet was recommended. Five years before admission, subtotal thyroid gland resection had been performed for goiter. The patient did well until 1995, when she developed rheumatoid arthritis, which was treated with cortisone and methotrexate.
Chitotriosidase determination
EDTA plasma samples were drawn from the patient and immediately frozen at −20°C. Chitotriosidase activity was determined as described earlier (12) with some minor modifications. The EDTA plasma was diluted 10 times with phosphate-buffered saline containing 1 mg/ml bovine serum albumin (BSA). The chitotriosidase activity was measured by incubation of 10 μl of diluted EDTA plasma with 100 μl of 4-methylumbelliferyl-β-D-N,N′,N″-triacetylchitotriose (Sigma) as substrate in citrate/phosphate buffer
Results
Chitotriosidase activity was increased to 827 nmol/ml plasma/h in this CESD patient, representing a 27-fold increase over control values (mean 30±20 nmol/ml/h, n=50, range 7–124), but far below the excessive increases of chitotriosidase activity found in adult symptomatic Gaucher type I patients (21 397±15 203 nmol/ml/h, n=47, range 2085–74 173).
Cultured fibroblasts from a skin biopsy were assayed for β-glucocerebrosidase and sphingomyelinase activity using radiolabeled lipid substrates as
Discussion
In a patient with hepatosplenomegaly and anemia, the presence of lysosomal storage disease was suggested by: a) the absence of malignancy, primary hematologic or liver disease, b) the presence of sea-blue histiocytes and vacuolation of macrophages and plasma cells in bone marrow smears, and c) an increase in plasma chitotriosidase activity.
The patient was finally diagnosed with cholesteryl ester storage disease (CESD) by: (i) the accumulation of cholesteryl esters found in fibroblast cultures,
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