Jing Pang1, Andrew C Martin2,3, Timothy R Bates1,4, Amanda J Hooper1,5, Damon A Bell1,5,6, John R Burnett1,5,6, Richard Norman7, Gerald F Watts1,6. 1. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia. 2. Department of General Paediatrics, Princess Margaret Hospital for Children, Perth, Western Australia, Australia. 3. School of Paediatrics and Child Health, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia. 4. St John of God Midland Public and Private Hospitals, Perth, Western Australia, Australia. 5. Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia. 6. Lipid Disorders Clinic, Cardiometabolic Services, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. 7. School of Public Health, Curtin University, Perth, Western Australia, Australia.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Ari E Horton; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Nicola K Poplawski; David Sullivan; Tom Brett; Clara K Chow; Stephen J Nicholls; Jing Pang; Gerald F Watts Journal: J Paediatr Child Health Date: 2022-07-15 Impact factor: 1.929
Authors: Gerald F Watts; David R Sullivan; David L Hare; Karam M Kostner; Ari E Horton; Damon A Bell; Tom Brett; Ronald J Trent; Nicola K Poplawski; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Clara K Chow; Jing Pang Journal: Am J Prev Cardiol Date: 2021-02-04