A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free cholesterol on HDL to cholesterol ester and allows the maturation of HDL. LCAT deficiency does not allow for HDL maturation resulting in its rapid catabolism of circulating apoA-1 and apoA-2. The remaining form of HDL resembles nascent HDL. Symptoms of the familial form include diffuse corneal opacities, target cell hemolytic anemia and proteinuria with renal failure. Fish eye disease only causes progressive corneal opacification.
Renal failure is the major cause of morbidity and mortality in complete LCAT deficiency, while in partial deficiency (fish eye disease) major cause for morbidity is visual impairment due to corneal opacity. These patients have low HDL cholesterol but surprisingly premature atherosclerosis is not seen. However, there are some reported cases.
In complete LCAT deficiency patients may present with Anemia, Corneal opacities, Hepatosplenomegaly, renal insufficiency while in partial deficiency (fish eye disease) corneal opacities is the main finding with hepatosplenomegaly.
Battery of tests are required such as CBC for anemia, kidney functions, urine for proteinuria, Lipid profile, these patients have very low HDL cholesterol and high triglyceride level, High free cholesterol and low cholesterol esters levels. However definitive diagnosis rest with LCAT gene analysis for mutation and functional activity.