Familial Lecithin Cholesterol Acyl Transferase Deficiency Syndromes

Lecithin cholesterol ester transferase (LCAT) is the sole enzyme in the circulation that mediates the esterification of free cholesterol (FC) to cholesterol ester (CE) in lipoproteins. Mutations in the LCAT gene result in one of two clinical syndromes: complete LCAT deficiency syndrome, and “fish eye disease.” The former is characterized by a broad spectrum of clinical features, including profound high-density lipoprotein (HDL) deficiency, hypertriglyceridemia, corneal opacities, anemia, neuropathies, and nephropathy. In contrast, fish eye disease patients develop severe HDL deficiency and severe corneal opacities, but the nervous system and kidneys are typically unaffected. Whether there is a predisposition to accelerated coronary heart disease with LCAT deficiency remains controversial. Currently, severe corneal opacities may be treated with corneal transplant. Only anecdotal evidence is available for preventive measures of progressive renal complications. LCAT replacement therapies are under investigation.