Acıbadem Mehmet Ali Aydınlar University School of Medicine, Department of Medical Biology, İstanbul, Turkey.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Clin Lipidol. 2018 Jul-Aug;12(4):863-867. doi: 10.1016/j.jacl.2018.04.008. Epub 2018 Apr 26.
This is a case report of a 38-year-old Syrian refugee male with early-onset extensive atherosclerosis. The physical and laboratory examination were remarkable with severe xanthomas in the upper and lower extremities and with low-density lipoprotein cholesterol (LDL-C) 417 mg/dL, total cholesterol 495 mg/dL, high-density lipoprotein cholesterol 30 mg/dL, and triglycerides 242 mg/dL. LDL-C level responded poorly to the high-dose statin treatment. The genetic analysis indicated that the patient had a large homozygous deletion in LDL receptor gene including the exons 7-14. A 12-kb deletion had occurred between the 2 Alu repetitive sequences that were oriented in opposite directions, one in intron 6 and the other in intron 14. This deletion eliminated exons 7-14, which exactly corresponded to the entire exon sequence coding the epidermal growth factor precursor homology domain. This deletion in LDL receptor was previously reported. This rare case of homozygous familial hypercholesterolemia presenting with multiple large and widely distributed xanthomas implicates the need for novel treatment options in familial hypercholesterolemia patients. The case is a Syrian refugee and emphasizes the urgent need to address orphan disease in refugee populations throughout the world.
这是一例 38 岁叙利亚难民男性早发广泛动脉粥样硬化的病例报告。该患者体格检查和实验室检查结果显著，四肢有严重的黄色瘤，低密度脂蛋白胆固醇（LDL-C）417mg/dL，总胆固醇 495mg/dL，高密度脂蛋白胆固醇 30mg/dL，甘油三酯 242mg/dL。尽管给予大剂量他汀类药物治疗，LDL-C 水平仍反应不佳。基因分析表明，该患者 LDL 受体基因存在大片段纯合缺失，包括外显子 7-14。在两个方向相反的 Alu 重复序列之间发生了 12kb 的缺失，一个位于内含子 6，另一个位于内含子 14。该缺失消除了外显子 7-14，正好对应编码表皮生长因子前体同源结构域的整个外显子序列。该 LDL 受体缺失此前已有报道。这种罕见的纯合子家族性高胆固醇血症病例表现为多发性大而广泛分布的黄色瘤，提示需要为家族性高胆固醇血症患者提供新的治疗选择。该病例是一名叙利亚难民，强调了在全世界难民群体中解决孤儿病的迫切需要。
