Familial lecithin-cholesterol acyltransferase: identification of heterozygotes with half-normal enzyme activity and...

Lecithin-cholesterol acyltransferase (LCAT) mass and activity was measured in Canadian kindred of Italian and Swedish descent with familial LCAT deficiency. Four subjects had LCAT mass of 5.21 +/- 0.87 micrograms/ml (mean +/- SD) and LCAT activity of 98.8 +/- 12.0 nmol/h/ml, well within their respective normal ranges. Five family members, including the parents, the maternal grandmother, and two of four siblings of the LCAT deficient subjects, had enzyme mass (2.85 +/- 0.32 micrograms/ml) and activity (50.8 +/- 6.3 nmol/h/ml) approximately one-half that of normal levels. These presumed heterozygotes had normal levels of apolipoproteins A-I, A-II, B and D. The two subjects with LCAT deficiency had no detectable LCAT mass (below 0.1 microgram/ml) or LCAT activity (below 0.76 nmol/h/ml), apolipoprotein A-I and D levels approximately 50% of normal, and apolipoproteins B and A-II levels only 30-35% of normal. LCAT deficiency in this family is determined by an autosomal recessive mode. Furthermore, LCAT levels and activity are determined by two autosomal codominant alleles, LCATn, the normal LCAT gene, and LCATd, the LCAT deficiency gene.