Louter Leonora, Defesche Joep, Roeters van Lennep Jeanine
Department of Internal Medicine, Division Vascular Medicine, Erasmus MC, Rotterdam, The Netherlands.
Department of Clinical Genetics, Division Vascular Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Atheroscler Suppl. 2017 Nov;30:77-85. doi: 10.1016/j.atherosclerosissup.2017.05.019. Epub 2017 Jun 1.
Familial Hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the LDLR gene, resulting in elevated serum cholesterol levels and elevated risk of premature cardiovascular disease (CVD). Timely treatment with lipid lowering medication can lower the risk of CVD to the same level of the normal population. Currently the incidence of FH is estimated at 1 in 240 persons in the Caucasian population. A diagnosis of FH can be made on the basis of clinical criteria (including LDL cholesterol and family history) or DNA testing. When a mutation is known within a family an unequivocal diagnosis can be made by DNA testing in family members at any age. Genetic cascade screening is a cost-effective way to identify patients and prevent CVD. Between 1994 until 2014 a nationwide and government subsidized cascade screening program functioned to identify FH patients in the Netherlands. During this time more than 28,000 patients with FH have been identified and entered in a central, national database. Since 2014 cascade screening has been integrated in the regular Dutch health care system. Screening, counseling and treatment are now integrated in the care as a whole of FH patients and families, coordinated by the treating physician, while the national FH database is still maintained. However, since cascade screening by actively approaching family members cannot be applied anymore because of new regulations within the healthcare system, the number of family members participating in the cascade screening program, has plummeted. With this review we would like to highlight the practical consequences of implementing and executing a cascade screening program with a special focus on the lessons learned in the Netherlands.
家族性高胆固醇血症（FH）是一种常染色体显性疾病，主要由低密度脂蛋白受体（LDLR）基因突变引起，导致血清胆固醇水平升高以及过早发生心血管疾病（CVD）的风险增加。及时使用降脂药物治疗可将心血管疾病风险降低至与正常人群相同的水平。目前，在白种人群中，FH的发病率估计为每240人中有1人。FH的诊断可基于临床标准（包括低密度脂蛋白胆固醇和家族史）或DNA检测。当一个家族中已知存在突变时，可通过对任何年龄的家庭成员进行DNA检测做出明确诊断。基因级联筛查是识别患者并预防心血管疾病的一种经济有效的方法。1994年至2014年期间，荷兰开展了一项由政府资助的全国性级联筛查项目，以识别FH患者。在此期间，已识别出超过28,000例FH患者并录入了一个中央国家数据库。自2014年以来，级联筛查已纳入荷兰常规医疗保健系统。目前，筛查、咨询和治疗已整合到FH患者及其家庭的整体护理中，由主治医生协调，同时国家FH数据库仍在维护。然而，由于医疗保健系统的新规定，不再能够通过主动联系家庭成员进行级联筛查，参与级联筛查项目的家庭成员数量大幅下降。通过本综述，我们想强调实施和执行级联筛查项目的实际影响，特别关注在荷兰吸取的经验教训。
