Yuan Yuan, Zhao Xiaoyan, Teng Xiangyun, Zhang Yunfeng
Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Ann Transl Med. 2021 Jan;9(2):180. doi: 10.21037/atm-20-5600.
Familial hypercholesterolemia (FH) is one of the most common inherited metabolic disorders characterized by elevated low-density lipid cholesterol (LDL-C) levels that lead to coronary artery disease at an early age and a low occurrence of cerebrovascular disease. Low-density lipoprotein receptor () gene mutation is the most common cause of FH. Here, we report a case of a 47-year-old woman who had multiple carotid artery stenosis and brain ischemic foci, an elevated level of LDL-C, underwent eyelid xanthoma excision, and a family history of hyperlipidemia. Thereafter, she was diagnosed with FH according to the Dutch Lipid Clinical Network criteria and whole genome sequencing revealed compound heterozygous mutations. However, she denied a history of coronary heart disease (CAD). The patient underwent stenting of the right subclavicular artery and right internal carotid artery in our hospital. Lipid-lowering drugs were also administered to prevent stroke recurrence. During a 3-year follow-up, the blood lipid level of the patient reduced, and the condition of intracranial and extracranial vascular stenosis improved. Furthermore, a cascade screening was performed in her pedigree, and 7/9 family members were found to have elevated LDL-C, 6/7 were found to carry one of the two LDLR variants detected in the proband, and in 4/6, the carotid intima-media thickness was ≥1 mm, which was predicted as a high risk factor of cerebrovascular disease. Her relatives with high risks of cardiovascular or cerebrovascular diseases have been under lipid monitoring and management of risk factors since then. To date, no cardiovascular or cerebrovascular event has been reported. In conclusion, this case reminds us to consider FH screening in early-onset stroke or transient ischemic attack patients with elevated LDL-C level. Our report also demonstrates the beneficial role of genetic testing and cascade screening in the relatives of FH patients.
家族性高胆固醇血症（FH）是最常见的遗传性代谢紊乱疾病之一，其特征是低密度脂蛋白胆固醇（LDL-C）水平升高，这会导致早年发生冠状动脉疾病，且脑血管疾病发生率较低。低密度脂蛋白受体（LDLR）基因突变是FH最常见的病因。在此，我们报告一例47岁女性病例，该患者有多处颈动脉狭窄和脑缺血灶，LDL-C水平升高，接受了眼睑黄色瘤切除术，并有高脂血症家族史。此后，根据荷兰脂质临床网络标准，她被诊断为FH，全基因组测序显示为复合杂合突变。然而，她否认有冠心病（CAD）病史。该患者在我院接受了右锁骨下动脉和右颈内动脉支架置入术。还给予了降脂药物以预防中风复发。在3年的随访中，患者的血脂水平降低，颅内和颅外血管狭窄情况改善。此外，对其家系进行了级联筛查，发现9名家庭成员中有7名LDL-C升高，7名中有6名携带先证者中检测到的两种LDLR变异之一，6名中有4名颈动脉内膜中层厚度≥1mm，这被预测为脑血管疾病的高危因素。从那时起，她患有心血管或脑血管疾病高风险的亲属一直在接受血脂监测和危险因素管理。迄今为止，尚未报告心血管或脑血管事件。总之，该病例提醒我们，对于LDL-C水平升高的早发性中风或短暂性脑缺血发作患者，应考虑进行FH筛查。我们的报告还证明了基因检测和级联筛查在FH患者亲属中的有益作用。
