1. Universal Screening for Familial Hypercholesterolemia in Children in Kagawa, Japan
- Author
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Masa-aki Kawashiri, Tomohiro Hirao, Jun Kunikata, Tsuyoshi Sasaki, Keiji Matsunaga, Takuji Fujisawa, Kazushige Dobashi, Yoichi Hoshikawa, Katsunori Yokoyama, Shigeru Ito, Takashi Kusaka, Ichiro Yokota, Asako Mizobuchi, Shohei Ishikawa, Hayato Tada, Takashi Iwase, Tetsuo Minamino, and Hai Ying Fu
- Subjects
Pediatrics ,medicine.medical_specialty ,Apolipoprotein B ,Familial hypercholesterolemia ,medicine.disease_cause ,Hyperlipoproteinemia Type II ,Japan ,Internal Medicine ,medicine ,Humans ,Child ,Apolipoproteins B ,Genetic testing ,Lipoprotein cholesterol ,Mutation ,medicine.diagnostic_test ,biology ,business.industry ,Biochemistry (medical) ,Genetic disorder ,Area under the curve ,Cholesterol, LDL ,Lipid screening ,medicine.disease ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,business - 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.
- Published
- 2022