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Norum disease and fish-eye disease are discussed as a single entry in this database because they are both caused by mutations in the same gene (LCAT). Most patients are diagnosed as young adults. Corneal opacities are may be the only clinically significant abnormality in fish-eye disease whereas anemia and renal complications are more significant in Norum disease. Lipid deposition in the cornea is responsible for the corneal opacities and may cause significant reduction in vision. However, opacities are concentrated near the limbus. The cornea in fish-eye disease has twice the normal amount of cholesterol and vacuoles in the stroma and Bowman’s. Vision ranges from 20/40 to hand motions, with onset in the first two decades and progression throughout life. The opacities form a mosaic pattern of small dot-like grey-white-yellow opacities. The fish-eye designation comes from the corneal clouding resembling boiled fish eyes.
Lecithin:cholesterol acyltransferase (LCAT) is a disorder of lipoprotein metabolism resulting in reduced plasma cholesterol esterifying activity. The mutation leading to Norum disease causes normocytic hemolytic anemia with significant proteinuria secondary to renal failure. However, patients with fish-eye disease do not have anemia or renal disease. Red blood cells may have increased cholesterol content and foam cells are found in bone marrow and in the glomerular tufts of the kidney. Peripheral neuropathy is sometimes present. Circulating cholesterol, triglycerides and phospholipids are elevated whereas high-density lipoprotein (HDL), apoA-I and apoA-II are reduced. However, premature atherosclerosis is not a feature contrary to expectations.
Complete LCAT deficiency (Norum) disease and partial deficiency (fish-eye disease) are autosomal recessive disorders secondary to mutations in the LCAT gene located on chromosome 16 (16q22.1). The mutation is located in codon 123 in fish-eye disease and in codon 4 of Norum disease.
Severe visual impairment is an indication for corneal transplantation. Renal failure may require renal transplantation.