Deficiency of apolipoproteins a‐i and c‐iii and severe coronary heart disease

Abstract

Summary: A 55-year-old woman with severe coronary arteriosclerosis and skin xanthomas is described. The patient had a normal total cholesterol level of 168 mg/dl. Her level of high-density lipoprotein cholesterol was markedly reduced (3 mg/dl). On apolipoprotein analysis, apolipoproteins A-I and C-III were not detectable, and the level of apolipoprotein A-I1 was found to be at a low level (3.5 mg/dl). This case may possibly belong to a distinct new disease entity of deficiencies of apolipoprotein A-I and C-111 in which coronary arteriosclerosis appears prematurely and severely.

Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia.

“…The clinical manifestations of one homozygote sister (II-c) included arcus cornealis, planar xanthomata, and premature CHD. Although planar xanthoma and/or corneal abnormalities appeared to distinguish subjects with severe HDL defi-A B ciency among a number of other kindreds reported (15)(16)(17)(18)(19)(20)(21)(22)(23)26), this appears not to be the case in our kindred. All of the remaining homozygotes, though not available for detailed clinical examination, were contacted and had no complaints related to CHD, neuropathy, or visual impairment.…”

“…Two kindreds with combined deficiency of apoA-I and apoC-III, one due to apoA-I and apoC-III gene inversion defect ( 15,16) and the other due to deletion of the entire apoA-I-CIII-AIV gene complex ( 17,18), rendering the individuals unable to synthesize apoA-I and apoC-III in the former case and additional apoA-IV synthetic defect in the latter case, appeared most susceptible to premature CHD. A Japanese family with an apoA-I gene codon 84 nonsense mutation ( 19,20) and a presumed HDL assembly defect also appeared to be susceptible. Our kindred, with an isolated apoA-I synthetic defect also confirms this association with CHD.…”

“…A number of kindreds with hereditary analphalipoproteinemia (AAL) have known defects in the apoA-I gene (15)(16)(17)(18)(19)(20)(21)(22)(23) that result in virtual absence of plasma HDL. In some other kindreds, the molecular defect either does not involve the apoA-I gene (24,25) or has yet to be identified (26)(27)(28)(29).…”

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

“…This kindred was described as having familial APOA1/C3 deficiency. A second kindred with premature CHD, marked HDL deficiency, and absence of apoA-I and apoC-III in plasma has also been described (15).…”

“…Marked HDL deficiency states (HDL cholesterol , 5 mg/dl) and undetectable plasma apolipoprotein A-I (apoA-I) levels have been reported in humans as a result of mutations at the APOA1/C3/A4 gene locus (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Such patients lack apoA-I-containing HDL in plasma, with normal or decreased triglyceride levels, normal LDL cholesterol levels, and often strikingly premature CHD (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Other patients with marked HDL deficiency have mutations affecting the apoA-I sequence that can affect the activity of lecithin:cholesterol acyl transferase activity (19)(20)(21)(22)(23)(24)(25)(26).…”