LCAT deficiency

Lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism caused by mutations in the LCAT gene located on chromosome 16q22.1. LCAT is an enzyme that esterifies free cholesterol in the blood, playing a critical role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. The disease exists in two forms: complete LCAT deficiency (also known as familial LCAT deficiency or Norum disease) and partial LCAT deficiency (also known as fish-eye disease). Both forms result in markedly reduced HDL cholesterol levels and accumulation of unesterified cholesterol in tissues. In complete LCAT deficiency, patients typically present in childhood or early adulthood with corneal opacities (diffuse corneal clouding), normochromic normocytic anemia (often with target cells), and progressive renal disease (proteinuria leading to nephrotic syndrome and eventually renal failure). Additional features may include hepatosplenomegaly and premature atherosclerosis, though the latter is variable. The corneal opacities are among the earliest signs and are present in virtually all affected individuals. Renal involvement, caused by lipid deposition in the glomeruli, is the most serious complication and the primary cause of morbidity and mortality. In partial LCAT deficiency (fish-eye disease), corneal opacities are the predominant finding, with renal disease and anemia typically absent or mild. There is currently no specific cure or enzyme replacement therapy approved for LCAT deficiency. Management is primarily supportive and includes renal protective strategies such as angiotensin-converting enzyme (ACE) inhibitors to slow proteinuria progression, dietary fat modification, and monitoring of renal function. Kidney transplantation may be necessary for patients who develop end-stage renal disease, although lipid deposition can recur in the transplanted kidney. Corneal transplantation has been performed for visual impairment, though recurrence of opacities in the graft is possible. Investigational approaches including recombinant LCAT enzyme replacement therapy are under study.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about LCAT deficiency