LIPA

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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:

  1. 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
  1. 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.

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