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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1866.)
© 2007 American Heart Association, Inc.

Letters to the Editor

Prevalence of Cholesteryl Ester Storage Disease

Sandro Muntoni; Heiko Wiebusch; Marianne Jansen-Rust; Stephan Rust; Udo Seedorf; Helmut Schulte; Klaus Berger; Harald Funke; Gerd Assmann

From the Department of Toxicology, Oncology, and Molecular Pathology Unit (S.M.), University of Cagliari, Italy; the Leibniz Institute of Arteriosclerosis Research (S.M., M.J.-R., S.R., U.S., H.S., H.F., G.A.), University of Münster, Germany; the Institute of Clinical Chemistry and Laboratory Medicine (H.W., G.A.), University Hospital Münster, Germany; the Department of Molecular Haemostaseology (H.F.), University of Jena, Germany; and the Institute of Epidemiology and Social Medicine (K.B.), University of Münster, Germany.

Correspondence to Sandro Muntoni, Dipartimento di Tossicologia, Sezione di Oncologia e Patologia Molecolare, Via Porcell 4, 09124 Cagliari, Italy. E-mail smuntoni@unica.it

Key Words: CESD • hyperlipidemia • low HDL-cholesterol • genetic analysis • lysosomal acid lipase

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cholesteryl ester storage disease (CESD) is an autosomal recessive chronic liver disease caused by lysosomal acid lipase (LAL) deficiency. The gene is located on chromosome 10q23.2-q23.3, and the enzyme is essential for triglycerides and cholesteryl ester hydrolysis in lysosomes. CESD is characterized by hypercholesterolemia, hypertriglyceridemia, HDL deficiency, and abnormal lipid deposition in many organs. In the liver this results in hepatomegaly caused by hepatic steatosis and fibrosis that can lead to micronodular cirrhosis.¹ Disease onset takes place during childhood or adolescence. Males and females are affected in about equal numbers. Patients rarely reach the age of 30. Biochemically, the disorder is recognized by largely reduced lysosomal acid lipase activity.^2,3 Complete absence of LAL activity causes Wolman Disease, which is normally fatal within the first 6 months of life.^1,4 Several groups have identified mutations in the LAL gene underlying CESD and Wolman disease.^5–9 Mutations causing Wolman disease produce an enzyme with no residual activity or no enzyme at all, whereas CESD-causing mutations encode for LAL which retains some enzyme activity.^4,10 A G-to-A transition at position –1 of the exon 8 splice donor (E8SJM, Exon 8 Splice Junction Mutation) leads to an in-frame deletion of exon 8. The resulting protein is 24 amino acids shorter and has no residual LAL activity, however E8SJM does not cause Wolman Disease because 2% to 4% of normally spliced LAL is present in homozygote carriers.^11,12 The vast majority of CESD patients described to date are E8SJM carriers.^3,11–17 This observation provided the possibility . . . [Full Text of this Article]