The LIPA gene at 10q24-q25 codes for the 399 amino acid pro-peptide of lysosomal acid lipase/cholesteryl ester hydrolase. This is responsible for the intracellular hydrolysis of cholesteryl esters and triglycerides that have been internalized via receptor-mediated endocytosis of lipoprotein particles. It has a role in mediating the effect of LDL (low density lipoprotein) uptake on suppression of hydroxymethylglutaryl-CoA reductase and activation of endogenous cellular cholesteryl ester formation.
Lysosomal acid lipase deficiency caused by mutations in LIPA manifests as either:
- Wolman disease
- Early-onset fulminant disorder of infancy
- Massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides
- Incidence of less than one in 100,000 live births
- Early death
- Cholesteryl ester storage disease (CESD)
- Milder, later-onset disorder
- Primary hepatic involvement by macrophages engorged with cholesteryl esters.
- Some early onset with severe cirrhosis
- Some progressive hepatic disease with survival into adulthood
Investigational treatment is being tried with sebelipase alfa.