Amelioration of circulating lipoprotein profile and proteinuria in a patient with LCAT deficiency due to a novel mutation (Cys74Tyr) in the lid region of LCAT under a fat-restricted diet and ARB treatment.

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a hereditary disease characterized by an abnormal lipid profile, corneal opacity, anemia and progressive renal disease. We report a patient with complete loss of LCAT activity due to a novel lcat gene mutation of Cys74Tyr in the lid region of LCAT protein. Esterification of cholesterol in this patient was disturbed by disruption of a substrate binding loop of Cys50-Cys74 in LCAT protein. She had progressive renal dysfunction, proteinuria, corneal opacity, anemia and an abnormal lipid profile. Her serum lipids showed a significant increase in abnormal lipoproteins at the original position in agarose gel electrophoresis and VLDL-cholesterol, and a severe decrease in serum HDL-cholesterol. Lipoprotein analyzes also revealed the presence of an abnormal midband lipoprotein, and a maturation disturbance of HDL particles. Renal function and proteinuria improved following the adoption of a fat-restricted diet and administration of an angiotensin II receptor blocker. The abnormal lipoproteins also decreased after this treatment.

Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency.

To study the metabolic abnormalities in familial lecithin-cholesterol acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and LCAT replacement therapy on plasma lipids and apolipoproteins were investigated in a patient with LCAT deficiency. The patient had elevated triglycerides (TG, 543.7 mg/dl) and phospholipids (PL, 350.3 mg/dl) and normal total cholesterol (TC, 206.9 mg/dl). Change to a low-fat diet reduced TC and TG by 20% and 75%, respectively. These reductions occurred mainly in the d < 1.006 fraction. At baseline, the patient had normal apolipoprotein B (apo B), low apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) and elevated apolipoprotein E (apo E). Long-term treatment with a low-fat diet increased plasma apoA-I and decreased apo E. However, urinary protein excretion did not change throughout the observed period. LCAT replacement with fresh frozen plasma (FFP) after the low-fat diet further reduced plasma apo E to the normal range. These results indicate that the elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT in the plasma, but also to fat intake. A low-fat diet may be effective in correcting lipid abnormalities. Moreover, plasma apo E may be a good indicator of the efficacy of diet therapy.