Lecithin:Cholesterol Acyltransferase ( LCAT ) Deficiency: Molecular Genetics

Abstract The lecithin:cholesterol acyltransferase (LCAT) enzyme is responsible for the synthesis of cholesteryl esters in human plasma and plays a critical role in high‐density lipoprotein (HDL) metabolism. Mutations in the LCAT gene leads to the development of two distinct syndromes, classical familial LCAT deficiency (FLD, OMIM 245900 ) and fish‐eye disease (FED, OMIM 136120 ). FLD and FED are rare disorders of lipoprotein metabolism, both characterised by low HDL cholesterol levels associated with multiple alterations in HDL structure and particle distribution. Clinical manifestations of the disease include corneal opacity, haemolytic anaemia and renal disease, which represents the major cause of morbidity and mortality in LCAT‐deficient cases. The pathogenesis of renal injury in LCAT deficiency is not understood. No cure presently exists for patients with genetic LCAT deficiency. Key Concepts: LCAT is the enzyme responsible of cholesterol esterification in plasma. Mutations in the LCAT gene lead to two rare diseases of lipid metabolism: Familial LCAT deficiency (FLD) and fish‐eye disease (FED). FLD and FED cases have very low HDL‐C levels in plasma, not necessarily associated with increased cardiovascular disease. Clinical manifestations of the disease include corneal opacity, hemolytic anemia, and renal disease. Renal disease represents the major cause of morbidity and mortality in homozygous carriers of LCAT deficiency.