Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
J Med Screen. 2019 Jun;26(2):71-75. doi: 10.1177/0969141318796856. Epub 2018 Oct 14.
To integrate child-parent screening and cascade testing into a single pathway-child-parent cascade screening (CPCS), for the identification of familial hypercholesterolaemia in the population and to estimate the number of new familial hypercholesterolaemia cases identified per child screened and the associated costs.
We applied the results from the published MRC Child-Parent Screening Study to 10,000 children, together with cascade testing first degree relatives of parents with a familial hypercholesterolaemia mutation identified by child-parent screening. We estimated the number of familial hypercholesterolaemia cases identified per child screened, the median cost per familial hypercholesterolaemia case identified and the median cost per child screened to identify one case using a range of cholesterol and familial hypercholesterolaemia mutation testing costs. We present a case study to illustrate the application of CPCS in practice.
CPCS identifies one new familial hypercholesterolaemia case per 70 children screened at a median estimated cost of £960 per new familial hypercholesterolaemia case or £4 per child screened. CPCS identifies an average of four new familial hypercholesterolaemia cases per family. In the case study, six new familial hypercholesterolaemia cases were identified, and preventive treatment started in five, with the index child expected to start when older.
CPCS for familial hypercholesterolaemia are complementary strategies. The sustainability of cascade testing relies on identifying new unrelated index cases. This is achieved with population-wide child-parent screening. Integrated CPCS is currently better than either method of familial hypercholesterolaemia detection alone. It has the potential to identify all, or nearly all, individuals with familial hypercholesterolaemia in the population at low cost.
将儿童-父母筛查和级联检测整合到单一途径-儿童-父母级联筛查（CPCS）中，以鉴定人群中的家族性高胆固醇血症，并估计每个被筛查儿童发现的新家族性高胆固醇血症病例数及其相关成本。
我们应用已发表的 MRC 儿童-父母筛查研究的结果，对 10000 名儿童进行了分析，并对通过儿童-父母筛查发现的家族性高胆固醇血症突变的父母的一级亲属进行了级联检测。我们估计了每个被筛查儿童发现的家族性高胆固醇血症病例数、每个被发现的家族性高胆固醇血症病例的中位数成本以及每个被筛查儿童的中位数成本，以确定一系列胆固醇和家族性高胆固醇血症突变检测成本。我们提供了一个案例研究，说明 CPCS 在实践中的应用。
CPCS 每筛查 70 名儿童即可发现 1 例新的家族性高胆固醇血症病例，估计每例新家族性高胆固醇血症病例的中位数成本为 960 英镑，或每筛查 1 名儿童的中位数成本为 4 英镑。CPCS 平均每例家庭可发现 4 例新的家族性高胆固醇血症病例。在案例研究中，发现了 6 例新的家族性高胆固醇血症病例，其中 5 例开始预防性治疗，预计当索引儿童年龄更大时开始治疗。
CPCS 是家族性高胆固醇血症的互补策略。级联检测的可持续性依赖于发现新的无关联索引病例。这是通过人群中的儿童-父母筛查来实现的。综合 CPCS 目前优于单独使用任何一种家族性高胆固醇血症检测方法。它有可能以低成本识别人群中所有或几乎所有的家族性高胆固醇血症患者。
