Clinical correlation
Human Lysosomal acid lipase (hLAL) hydrolyzes triacylglycerol to free fatty acids and glycerol, and cholesteryl esters to free cholesterol and fatty acids. It is a critical enzyme in cholesterol metabolism, serving to make available free cholesterol for the needs of cells. Cholesteryl ester storage disease (CESD) and Wolman’s disease are two distinct phenotypic forms of a genetic deficiency of hLAL; both are rare autosomal recessive diseases. Cholesteryl ester storage disease is usually diagnosed in elder person and is evidenced by hypercholesterolemia, hepatomegaly, and early onset of severe atherosclerosis. Affected individuals express hLAL activity but at a very low level (less than 5% normal). Apparently this level is sufficient to hydrolyze triacylglycerol but not cholesteryl esters. Analysis of the gene for the enzyme indicates that a mutation has occurred on both alleles at a splice junction leading to a catalytically defective and unstable enzyme.
Wolman’s disease is manifested in infants and is usually fatal by age one. There is no detectable activity of hLAL. Both triacylglycerol and cholesteryl esters accumulate in tissues. Gene analysis has demonstrated that a homozygous mutation leads to a gene product that cannot be translated into an active enzyme.