Clinical scores fail to sufficiently identify children with Familial Hypercholesterolemia

ABSTRACT

The study aimed to assess the effectiveness of three clinical diagnostic criteria (Simon Broome, MEDPED, and guideline-derived) in identifying children with familial hypercholesterolemia (FH) compared to genetic testing. The evaluation involved 1337 children with elevated LDL-C levels, focusing on the sensitivity and specificity of these clinical scores in detecting genetically confirmed FH cases.Clinical data were gathered by a self-reporting questionnaire. Clinical FH was defined in accordance with the tested FH score. Genetically confirmed heterozygous FH (HeFH) was defined by a (likely) pathogenic variant.Of 1337 children undergoing genetic analysis, 211 showed a pathogenic FH mutation. Applying SB, MP and GL-EAS criteria resulted in 210/1337, 125/1337 and 112/835 children being categorized to have FH clinically. The sensitivity of the clinical scores ranged from 0.44-0.54 with a positive predictive value (PPV) of 0.51-0.79. The specificity was 0.91-0.97 with a negative predictive value (NPV) of 0.89-0.91. Similar results were observed for the three clinical scores regarding sensitivity, specificity, PPV and NPV in subgroup analyses defined by gender, age (