Plasma lipoproteins of patients with genetic LAL deficiency are enriched in cholesteryl esters: Relevance of cholesterol esterification by LCAT

Lysosomal acid lipase (LAL) is responsible for cholesteryl ester hydrolysis in lysosomes. Aim of the study was to investigate the impact of LAL deficiency on lipoprotein composition and the relevance of LCAT as a source of cholesteryl esters accumulating in the lipoproteins of patients with cholesteryl ester storage disease (CESD). Methods: Lipid and lipoprotein profile, the composition of plasma lipoproteins and of cholesteryl ester (CE) fatty acids and plasma cholesterol esterification were assessed in CESD children and pediatric controls. Results: CESD cases presented with classical clinical and biochemical features of LAL deficiency, with moderate elevation of serum transaminases, ecographic evidence of hepatic steatosis, increased plasma levels of TC, LDL-C and TG, and reduced HDL-C. Enrichment of CE was evident in isolated VLDL, IDL and LDL (with a parallel reduction of TG content), but not in HDL. Cholesterol esterification by LCAT was preserved in CESD patients, as indicated by normal unesterified/total cholesterol ratio and LCAT activity, and by an even reduced content of preβ-HDL. The composition of fatty acid residues within plasma cholesteryl esters was comparable between patients and controls, supporting a preserved LCAT/ACAT ratio in the generation of cholesteryl esters; indeed, no differences were detected in the percentage of saturated and unsaturated fatty acids and in the oleate/linoleate ratio between CESD patients and Controls. Conclusions: LCAT could play a central role in the generation of cholesteryl esters accumulating in plasma lipoproteins and subsequently in the liver of patients with genetic LAL deficiency.