Hazzard W R, Miller N, Albers J J, Warnick G R, Baron P, Lewis B
Lancet. 1981 Feb 7;1(8215):298-301. doi: 10.1016/s0140-6736(81)91911-5.
A prepubertal girl with both homozygous isoapolipoprotein-E3 deficiency (the genetic defect underlying type-III hyperlipoproteinaemia) and heterozygous familial hypercholesterolaemia (familial type-IIa hyperlipoproteinaemia) presented with severe hypercholesterolaemia and antecubital and popliteal planar xanthomas. She responded dramatically to clofibrate. Her mother was normolipidaemic and heterozygous for apo-E3-deficiency. Her father, an obligate apo-E3-deficient heterozygote, and his similarly affected brother died prematurely with severe hypercholesterolaemia which had been refractory to clofibrate. Her paternal grandfather, who had the same combination of disorders as the proband, also responded to clofibrate, whereas her grandmother was normolipidaemic. Hence homozygous apo-E3 deficiency may present during childhood as severe hypercholesterolaemia when combined with familial hypercholesterolaemia, suggesting that the low-density-lipoprotein receptor may represent one mechanism whereby apo-E3-deficient remnants of very-low-density lipoproteins and chylomicrons are cleared from the plasma compartment. The removal of such apo-E3-deficient remnants is especially facilitated by clofibrate.
一名青春期前女孩，患有纯合子异载脂蛋白E3缺乏症（III型高脂蛋白血症的潜在遗传缺陷）和杂合子家族性高胆固醇血症（家族性IIa型高脂蛋白血症），出现严重高胆固醇血症以及肘前和腘平面黄色瘤。她对氯贝丁酯反应显著。她的母亲血脂正常，是apo-E3缺乏症的杂合子。她的父亲，一名必然的apo-E3缺乏症杂合子，以及他同样患病的兄弟，因严重高胆固醇血症而过早去世，且对氯贝丁酯治疗无效。她的祖父与先证者患有相同的疾病组合，对氯贝丁酯也有反应，而她的祖母血脂正常。因此，纯合子apo-E3缺乏症在儿童期与家族性高胆固醇血症合并时，可能表现为严重高胆固醇血症，这表明低密度脂蛋白受体可能是清除极低密度脂蛋白和乳糜微粒中apo-E3缺乏的残粒的一种机制。氯贝丁酯尤其有助于清除此类apo-E3缺乏的残粒。
