How are children and adolescents with familial hypercholesterolaemia detected globally? Analysis from the FHSC registry on over 11,800 participants from 48 countries

Background and Aims: Globally, heterozygous familial hypercholesterolaemia (HeFH) presents in 6.4 million children/adolescents. Early identification enables the opportunity for timely intervention, but population efforts have largely focused on detecting adults to identify children. With screening for FH in children/adolescents increasingly discussed worldwide, we aimed to understand the current unmet need across the FH diagnostic pathway globally, as required resources for detection may vary across health systems and by country-income status. Methods: Cross-sectional analyses at registry entry of <18-year-old children/adolescents with clinical and/or genetic diagnosis of HeFH from 48 countries. Homozygous FH individuals were excluded. Countries were classified by high- and non-high-income status in accordance to 2022 World Bank definition. Results: 11,848 children/adolescents were included in the analyses (96.4% from high-income; 50% girls); characteristics of participants are in table. 92.7% and 48.0% children/adolescents had a genetically confirmed diagnosis in high- and non-high-income regions respectively (p<0.001). Presence of corneal arcus, xanthomas, and coronary artery disease (CAD) were 2.8-times, 7.6-times, and 38-times higher in non-high-vs. high-income regions. LDL-C not on lipid-lowering medications (LLM) were 0.89 mmol/L higher in non-high-vs. high-income regions (p<0.001). The odds of having LDL-C not on LLM (>7.80 mmol/L) was 72% lower in high-income-regions. Conclusions: Identification of FH across non-high-vs. high-income-regions is much lower. Genetic diagnosis in non-high-income regions is used less frequently (likely, at least partly, due to unavailability and/or inaccessibility of genetic testing), hence there is a higher reliance on clinical criteria among non-high-income-regions which leads to higher odds of children/adolescents being detected with a more severe phenotype (namely physical signs, CAD and LDL-C).