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Introduction: Familial hypercholesterolemia (FH) is an autosomal hereditary disease found in patients who have elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. Early detection and treatment of FH during childhood potentially reduces the risk of premature cardiovascular events. In Kagawa prefecture, a unique community health system, involving three steps, has been conducted to prevent lifestyle-related diseases for 10-year-old children. This system includes universal lipid screening, selection by pediatricians, and next-generation sequencing (NGS) of FH-related genes in the hospitals. The aim of this study is to investigate whether this system can be effective in detection of FH. Methods: In Kagawa prefecture, the universal lipid screening of children at 10 years of age is performed annually at school, covering over 90% of the target group. After excluding secondary hypercholesterolemia, pediatric clinics introduced children with LDL-C levels >140 mg/dL to four hospitals to perform NGS to detect FH. Results: In 2017, 279 children (3.7%) showed elevated LDL-C >140mg/dL among 7,647 ones who received the screening. We performed NGS for 46 children after excluding secondary hypercholesterolemia by pediatricians (LDL-C 186.0±50.3 mg/dL; M/F 27/19) and 26 children (57%) had FH genetic mutations (23 LDL-R, 3 PCSK9). The children with LDL-C >180mg/dL are recommended to receive statin therapy according to the guideline from the Japanese Atherosclerosis Society (JAS). Children with LDL-C levels ≥180 mg/dL have 74% of positive genetic mutations, and even those with 140-180 mg/dl LDL-C levels have as much as 44%, respectively (Table). Conclusions: The unique community health system in Kagawa can efficiently detect FH of children. Further investigation will be required for the effective prevention of future atherosclerotic cardiovascular diseases.

Introduction: Familial hypercholesterolemia (FH) is an autosomal hereditary disease found in patients who have elevated low-density lipoprotein cholesterol (LDL-C) from birth. Early detection and treatment of FH during childhood potentially reduces the risk of premature cardiovascular events. In Kagawa prefecture, a unique community health system, involving three steps, has been conducted to prevent lifestyle-related diseases for 10-year-old children. This system includes universal lipid screening, selection by pediatricians, and next-generation sequencing (NGS) of FH-related genes in hospitals. The aim of this study is to compare 3 international guidelines to detect pediatric FH with this unique community health system in Kagawa. Methods: In Kagawa prefecture, the universal lipid screening of approximately 8,000 children at 10 years of age is performed annually, covering over 90% of the target group. After excluding secondary hypercholesterolemia, pediatric clinics introduced children with LDL-C >140mg/dL to 4 designated hospitals to perform NGS. We applied the guidelines of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), and the Japanese Atherosclerosis Society (JAS) to children who received NGS in the unique community health system in Kagawa. Results: We performed NGS for 46 children from January 2018 to February 2020 (LDL-C 186.0±50.3 mg/dL; Male/F 27/19) and 26 (57%) had FH genetic mutations (23 LDL-R and 3 PCSK9 mutations). Seventeen children met FH criteria for DLCN (35%), 10 for Simon Broome (22%), and 11 for JAS (24%), respectively. The combination of NGS and either of the 3 guidelines increased the number of children diagnosed as FH up to 31 (67%). Conclusion: International guidelines detected only half of pediatric FH who were diagnosed by the unique community health system in Kagawa. Further investigation will be required to build an effective universal screening system for pediatric FH.