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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Familial Hypercholesterolemia ; Clinical Scores ; Genetic Testing ; Prevention ; Screening; Diagnosis; Population; Statins; Risk; Care
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2047-4873
e-ISSN 2047-4881
Journal European Journal of Preventive Cardiology
Publisher Sage
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503292-001
Grants
Bayerisches Staatsministerium fur Gesundheit, Pflege und Prevention (Bavarian State Ministry of Health, Care and Prevention) StMGP
DOI 10.1093/eurjpc/zwaf301
WOS ID 001541568100001
PubMed ID 40632909
Erfassungsdatum 2025-07-18
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