Schmieder Raphael S, Krefting Johannes, Ates Sara, Schlieben Lea D, Arens Stefan, Kordonouri Olga, Sander Michaela, Holdenrieder Stefan, Mall Volker, Meitinger Thomas, von Scheidt Moritz, Koenig Wolfgang, Leipold Georg, Prokisch Holger, Schunkert Heribert, Sanin Veronika
Department of Cardiology, Deutsches Herzzentrum München, Klinikum der Technischen Universität München, Munich, Germany.
Deutsches Zentrum für Herz- und Kreislauferkrankungen (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
Eur J Prev Cardiol. 2025 Jul 9. doi: 10.1093/eurjpc/zwaf301.
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 (<10 years vs ≥10 years), or weight (≥90th BMI-percentile vs <90th BMI-percentile).
Clinical FH scores offer a high degree of specificity for FH diagnosis in children, but at the expense of low sensitivity. Specifically, half of the mutation-positive children in this study would have been missed for early diagnosis and preventive treatment. Given the widespread availability of affordable genetic testing such analysis should be performed at a lower threshold than that indicated by these clinical scores.
