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Schmieder, R.S.* ; Krefting, J.* ; Ates, S.* ; Schlieben, L.D. ; Arens, S.* ; Kordonouri, O.* ; Sander, M.* ; Holdenrieder, S.* ; Mall, V.* ; Meitinger, T.* ; von Scheidt, M.* ; Koenig, W.* ; Leipold, G.* ; Prokisch, H. ; Schunkert, H.* ; Sanin, V.*

Clinical scores fail to sufficiently identify children with Familial Hypercholesterolemia.

Eur. J. Prev. Cardiol., DOI: 10.1093/eurjpc/zwaf301 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Familial Hypercholesterolemia ; Clinical Scores ; Genetic Testing ; Prevention ; Screening; Diagnosis; Population; Statins; Risk; Care
ISSN (print) / ISBN 2047-4873
e-ISSN 2047-4881
Zeitschrift European Journal of Preventive Cardiology
Verlag Sage
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen
Bayerisches Staatsministerium fur Gesundheit, Pflege und Prevention (Bavarian State Ministry of Health, Care and Prevention) StMGP