Universal paediatric screening for familial hypercholesterolaemia: Lessons learnt from our pilot study EARLIE

Background and aims Universal screening for familial hypercholesterolaemia (FH) has been proposed; but implementation remains limited. This pilot study assesses the feasibility and efficacy of a screening based on a capillary blood test in children during a school medical visit. Additionally, we review published screening strategies and cut-off values. Methods Screening consisted of a questionnaire and capillary blood test in children aged 7-12 years. Further diagnostic work-up (fasting blood test under low-cholesterol diet and genetic analysis) was proposed if total cholesterol (TC) > 230 mg/dL (>5.9 mmol/L) and/or low-density lipoprotein cholesterol (LDL) > 160 mg/dL (>4.1 mmol/L). If FH was confirmed, the child was commenced on lipid-lowering therapy, and reverse cascade screening was performed within the family. Results 1860 children of 3733 invited children participated (49.8%). 30 refused the blood test (1.6%). Median TC was 158 mg/dL (4.1 mmol/L; Q25/75,141/174 [3.6/4.5]; P99 230 [5.9]); median LDL 74 mg/dL (1.9 mmol/L; 61/89 [1.6/2.3]; 139 [3.6]). Recall rate 1%. In the sub-cohort with LDL >160 mg/dL (>4.1 mmol/L), (n = 6): detection of three pathogenic variants and five additional affected family members, while three declined further follow-up. Conclusions FH screening based on a capillary lipid panel is an efficient screening method. However, 50% of highly suspicious cases declined further follow-up. We therefore advocate screening in the presence of parents to allow discussion of the results and explanation of further diagnostic work-up and long-term health risks. Cut-off levels should be adapted to the methodology used and re-evaluated during the course of the screening programme.