Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Children's Hospital Auf der Bult, Janusz-Korczak-Allee, Hanover, Germany.
Genet Med. 2022 Oct;24(10):2103-2111. doi: 10.1016/j.gim.2022.06.010. Epub 2022 Aug 1.
In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation.
We analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents.
A total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child-parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472).
Universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.
在欧洲，目前有超过 200 万的家族性高胆固醇血症（FH）患者未被诊断。迫切需要有效的 FH 儿童诊断筛查策略。我们评估了两种不同 FH 儿童筛查方案的整体表现：采用选择性和非选择性参与的普筛方案。
我们分析了来自 2 个独立人群的数据，这些人群共筛查了超过 166000 例高胆固醇血症患者。对 945 名儿童和 99 名父母的 FH 相关基因进行了基因分析。
共有 305 名（32.3%）儿童的 FH 相关基因检测结果为阳性或意义不明的变异。对于低密度脂蛋白胆固醇水平为 3.5 mmol/L（135.3 mg/dL），确认 FH 的总体敏感性和特异性分别为 90.5%和 55.3%。作为儿童-父母筛查的一部分，在>90%的家庭中，报告胆固醇水平较高的父母携带家族遗传变异。从非选择性普筛方案中得出的 FH 队列患病率估计为每 431 人中就有 1 人（95%CI=1/391-1/472）。
在儿童中采用 3 步 FH 普筛方法，可以以合理的成本检测到每一代接受筛查的大多数儿童及其父母。非选择性筛查策略可能优于选择性筛查策略。
