This study describes a variant of familial
apoA-I deficiency associated with a moderate risk for premature
coronary artery disease. The proband, a 25-year-old man of Philippine origin, and his 62-year-old maternal aunt had peripheral corneal opacification, xanthelasma, and planar
xanthoma; the aunt had
coronary artery bypass surgery at 61 years of age. Proband's parents and three brothers were asymptomatic and apparently healthy. The characteristic
apolipoprotein features of affected patients were the immunochemically and chemically undetectable
apoA-I, reduced levels of
apoA-II,
apoC-II,
apoC-III, and apoD, and normal levels of
apoB and
apoE; except for negligible levels of
high density lipoprotein (
HDL)-cholesterol (2-3 mg/dl), their plasma
lipid profile was normal. The
apoA-I levels in all five unaffected relatives were more than one SD below the normal mean values for their age and sex; the
HDL-cholesterol levels of proband's unaffected brothers were below the 10th percentile of normal control values. Patient's
very low density lipoprotein (VLDL),
low density lipoprotein (
LDL), and HDL contained 1.4, 80.4, and 18.1%, whereas those of control subjects contained 2.7, 28.8, and 68.1% of the total
apolipoprotein mass, respectively. In unaffected relatives, the levels of LP-A-I, but not LP-A-I:A-II, were significantly lower than in controls. Neither of the two patients had detectable concentrations of LP-A-I or LP-A-I:A-II. Their HDL only consisted of LP-A-II particles, the levels of which (7-13 mg/dl) were similar to those of unaffected relatives or controls. There was no difference in the
lipid composition of LP-A-II between patients and their relatives. However, LP-A-II from patients contained substantial amounts of
apoC-
peptides and
apoE (0.40-0.98 mg/mg
apoA-II), whereas those from unaffected relatives were free of these minor
apolipoproteins. In patients, among all four major
apoB-containing
lipoproteins, only the levels of LP-B and LP-B:C were slightly higher than those in controls. Results of this study suggest a genetic cause for this variant of
apoA-I deficiency characterized most probably by autosomal recessive inheritance. It appears that patients are likely to be homozygous for a gene present in single dose in the parents and brothers of the affected proband.(ABSTRACT TRUNCATED AT 400 WORDS)