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 Muta-tion) 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 to obtain a good estimate for the prevalence of CESD in the general population by performing a genetic E8SJM screening.

We therefore screened for the mutations in a test cohort of 1152 individuals from the PROCAM (PROspective CArdiovascular Münster)-Study of North-Western Germany and 2 validation cohorts, 1 from the city of Münster (PROCAM, n478) and 1 from the MEMO-Study18 cohort (n376), which is a follow-up of the WHO-MONICA project from Augsburg (Southern Germany). The study was approved by