Uauy R, Vega G L, Grundy S M
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9052.
J Clin Endocrinol Metab. 1991 Jan;72(1):179-87. doi: 10.1210/jcem-72-1-179.
A family is described in which the probands, twin girls, had severe hypercholesterolemia suggestive of familial hypercholesterolemia (FH). The mother of the twins had normal plasma cholesterol levels, and the father had only moderate hypercholesterolemia. Moreover, low density lipoprotein (LDL) binding studies in cultured fibroblasts and isolated lymphocytes in the parents failed to reveal significantly reduced LDL receptor activity that is typical of FH heterozygotes. Turnover studies of LDL in the parents, however, revealed low fractional clearance rates (FCRs) for LDL. In cultured fibroblasts and isolated lymphocytes from the twin probands, binding of normal LDL was half normal or less. LDL turnover studies in the twins revealed a marked reduction in FCRs for LDL. When the twins were treated with lovastatin, however, FCRs for LDL increased significantly, suggesting enhancement of LDL receptor activity. This finding along with LDL binding studies in the cultured cells infer that the twins did not have homozygous FH. In addition, all family members tested negative for familial defective apolipoprotein-B-100, and LDL isolated from the mother and twins showed normal binding to normal fibroblasts. The overall data suggest that the severe hypercholesterolemia in the offspring was due to inheritance of mild to moderate defects of LDL receptor function from both parents. Although the latter defects could not be detected with certainty by in vitro tests in each parent, they were evident from LDL turnover tests. Coinheritance of these defects apparently produced severe hypercholesterolemia in the offspring.
本文描述了一个家族，先证者为一对双胞胎女孩，患有严重高胆固醇血症，提示家族性高胆固醇血症（FH）。双胞胎的母亲血浆胆固醇水平正常，父亲仅有中度高胆固醇血症。此外，对父母培养的成纤维细胞和分离的淋巴细胞进行的低密度脂蛋白（LDL）结合研究未能发现FH杂合子典型的LDL受体活性显著降低。然而，对父母的LDL周转率研究显示，LDL的分数清除率（FCR）较低。在双胞胎先证者的培养成纤维细胞和分离的淋巴细胞中，正常LDL的结合量为正常水平的一半或更低。对双胞胎的LDL周转率研究显示，LDL的FCR显著降低。然而，当双胞胎接受洛伐他汀治疗时，LDL的FCR显著增加，提示LDL受体活性增强。这一发现以及在培养细胞中的LDL结合研究表明，双胞胎并非纯合子FH。此外，所有检测的家庭成员家族性缺陷载脂蛋白B-100均为阴性，从母亲和双胞胎分离的LDL与正常成纤维细胞的结合显示正常。总体数据表明，后代的严重高胆固醇血症是由于从父母双方遗传了轻度至中度的LDL受体功能缺陷。虽然通过体外试验无法在每位父母中确切检测到后者的缺陷，但从LDL周转率试验中可以明显看出。这些缺陷的共同遗传显然在后代中产生了严重的高胆固醇血症。
