Pang Jing, Martin Andrew C, Bates Timothy R, Hooper Amanda J, Bell Damon A, Burnett John R, Norman Richard, Watts Gerald F
School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
Department of General Paediatrics, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
J Paediatr Child Health. 2018 Jul;54(7):741-747. doi: 10.1111/jpc.13898. Epub 2018 Apr 6.
The aim of this study was to evaluate the clinical outcome of parent-child testing for familial hypercholesterolaemia (FH) employing genetic testing and the likely additional cost of treating each child.
Parent-child testing for gene variants causative of FH was carried out according to Australian guidelines. The number of new cases detected, the low-density lipoprotein (LDL)-cholesterol that best predicted a mutation and the proportional reduction in LDL-cholesterol following statin treatment was evaluated. Treatment costs were calculated as the cost per mmol/L reduction in LDL-cholesterol.
A total of 126 adult patients, known to have a pathogenic mutation causative of FH, and their children were studied. From 244 children identified, 148 (60.7%) were genetically screened; 84 children were identified as mutative positive (M+) and 64 as mutative negative. Six of the M+ children were already on statin treatment; 40 were subsequently treated with low-dose statins, with LDL-cholesterol falling significantly by 38% (P < 0.001). The estimated cost per mmol/L reduction of LDL-cholesterol of a child receiving statins from ages 10 to 18 years is AU$1361, which can potentially be cost-effective. An LDL-cholesterol threshold of 3.5 mmol/L had a sensitivity of 92.8% and specificity of 96.6% for the detection of a mutation.
Genetic testing of children of affected parents with FH is an effective means of detecting new cases of FH. Cascade testing can enable early statin therapy with significant reductions in LDL-cholesterol concentration.
本研究旨在评估采用基因检测进行家族性高胆固醇血症（FH）亲子检测的临床结果以及治疗每个孩子可能产生的额外费用。
根据澳大利亚指南对导致FH的基因变异进行亲子检测。评估检测到的新病例数量、最能预测突变的低密度脂蛋白（LDL）胆固醇水平以及他汀类药物治疗后LDL胆固醇的比例降低情况。治疗费用按每降低1 mmol/L的LDL胆固醇计算。
共研究了126名已知患有导致FH的致病突变的成年患者及其子女。在确定的244名儿童中，148名（60.7%）接受了基因筛查；84名儿童被确定为突变阳性（M+），64名儿童被确定为突变阴性。6名M+儿童已经在接受他汀类药物治疗；40名儿童随后接受了低剂量他汀类药物治疗，LDL胆固醇显著下降了38%（P < 0.001）。10至18岁接受他汀类药物治疗的儿童每降低1 mmol/L的LDL胆固醇估计费用为1361澳元，这可能具有成本效益。LDL胆固醇阈值为3.5 mmol/L时，检测突变的灵敏度为92.8%，特异性为96.6%。
对患有FH的父母的子女进行基因检测是检测FH新病例的有效手段。级联检测可实现早期他汀类药物治疗，显著降低LDL胆固醇浓度。
