Background and aim: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers.
Methods and results: We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males.
Conclusions: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.
Keywords: CESD; Cholesterol ester storage disease; E8SJM; E8SJM carriers; Genetic analysis; LAL; Lipids; Lysosomal acid lipase; cholesterol ester storage disease; exon 8 splice junction mutation; lysosomal acid lipase.
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