Keiji Matsunaga1, Asako Mizobuchi1, Hai Ying Fu1, Shohei Ishikawa2, Hayato Tada3, Masa-Aki Kawashiri3, Ichiro Yokota4, Tsuyoshi Sasaki5, Shigeru Ito6, Jun Kunikata7, Takashi Iwase8, Tomohiro Hirao9, Katsunori Yokoyama10, Yoichi Hoshikawa10, Takuji Fujisawa11, Kazushige Dobashi12, Takashi Kusaka8, Tetsuo Minamino1. 1. Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University. 2. Kinashi Obayashi Hospital. 3. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University. 4. Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Shikoku Medical Center for Children and Adults. 5. Department of Pediatrics, Mitoyo General Hospital. 6. Department of Pediatrics, Kagawa Prefectural Central Hospital. 7. Clinical Research Support Center, Kagawa University Hospital. 8. Department of Pediatrics, Faculty of Medicine, Kagawa University. 9. Department of Public Health, Faculty of Medicine, Kagawa University. 10. Department of Health and Welfare, Kagawa Prefectural Government. 11. Fujisawa Children's Clinic. 12. Department of Pediatrics, School of Medicine, University of Yamanashi.
Abstract
AIM: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. METHOD: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. RESULTS: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. CONCLUSION: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.
AIM: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. METHOD: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. RESULTS: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. CONCLUSION: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.