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Progress in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia
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摘要: 家族性高胆固醇血症(familial hypercholesterolemia，FH)是严重遗传代谢性疾病，临床上分为纯合和杂合两种类型，纯合型FH(homozygous FH，HoFH)发病率为1/(16万~100万)，被认为是罕见病。HoFH主要特点为极高水平的低密度脂蛋白胆固醇、多部位黄色瘤及早发动脉粥样硬化性心血管疾病，如不及时诊断、早期治疗, 青少年期即可发生心肌梗死甚至死亡。近年来，国际上也越来越重视FH的早期诊断和治疗，发布了多项FH指南与共识，我国亦结合国情制定了适合中国人的筛查诊断标准，为更好治疗FH提供了基础。本文就HoFH现有的诊断标准、鉴别诊断筛查和治疗方法进行综述，旨在提高医生对该病的认识。Abstract: Familial hypercholesterolemia (FH) is a serious hereditary metabolic disease. It is clinically divided into homozygous and heterozygous.The incidence of homozygous FH(HoFH) is 1/(160 000-1 000 000) and considered as a rare disease. HoFH is characterized by very high levels of low density lipoprotein cholesterol, multi-sited yellow tumors, and atherosclerosis cardiovascular disease. Without prompt diagnosis and early treatment, myocardial infarction and even death can occur in adolescence. In recent years, the international community has paid more and more attention to the early diagnosis and treatment of FH, and issued a number of guidelines and consensus on FH. China has also developed a screening and diagnostic standard suitable for Chinese people in combination with national conditions, which provides bases for better treatment of FH. This article reviewed HoFH's existing diagnostic criteria, differential diagnostic screening, and treatment methods, to improve physicians' understanding of the disease.
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Key words:
- familial hypercholesterolemia /
- rare disease /
- diagnostic criteria /
- treatment
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表 1 HoFH主要临床诊断标准
诊断标准 内容 美国心脏学会2015年关于FH议程的科学声明[8] 满足以下3个条件之一：
(1)LDL-C≥10 mmol/L且父母中至少一方为FH
(2)LDL-C≥10 mmol/L且小于20岁患者有皮肤/肌腱黄色瘤或主动脉瓣疾病
(3)如无家族史，患者LDL-C > 14 mmol/L (基因检测阳性时，LDL-C可 < 10 mmol/L)2014年欧洲动脉粥样硬化学会意见书：改善HoFH的检测与管理[9] 同时满足以下2个条件：
(1)治疗前LDL-C ≥13 mmol/L或治疗后LDL-C≥ 8 mmol/L
(2)10岁前出现皮肤/肌腱黄色瘤
若父母均为HeFH，儿童或成人患者治疗后血脂水平类似父母血脂水平不能排除HoFH诊断2014年英国关于HoFH的管理声明[10] 满足以下3个条件之一：
(1)儿童LDL-C > 11 mmol/L且10岁前出现皮肤/肌腱黄色瘤
(2)成人LDL-C > 13 mmol/L且有皮肤/肌腱黄色瘤
(3)血脂达到临床诊断标准且父母双方基因诊断均为HoFH2012日本动脉粥样硬化协会FH管理指南[11] 同时满足以下3个条件：
(1)父母为HeFH
(2)儿童期有早发ASCVD，特别是早发冠心病
(3)TC≥16 mmol/L并伴有皮肤/肌腱黄色瘤中国《临床冠心病学》[12] 同时满足以下2个条件：
(1)成人血清TC > 7.8 mmol/L或LDL-C > 4.4 mmol/L，16岁以下儿童TC > 6.7 mmol/L
(2)患者或亲属有肌腱黄色瘤FH：家族性高胆固醇血症；HoFH：纯合型家族性高胆固醇血症；HeFH：杂合型家族性高胆固醇血症；LDL-C：低密度脂蛋白胆固醇；TC：总胆固醇；ASCVD：动脉粥样硬化性心血管疾病 
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