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Universal screening for familial hypercholesterolemia in 2 populations

  • Ursa Sustar
    Affiliations
    Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia

    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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  • Olga Kordonouri
    Affiliations
    Children’s Hospital Auf der Bult, Janusz-Korczak-Allee, Hanover, Germany
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  • Matej Mlinaric
    Affiliations
    Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
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  • Jernej Kovac
    Affiliations
    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Clinical Institute of Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
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  • Stefan Arens
    Affiliations
    Children’s Hospital Auf der Bult, Janusz-Korczak-Allee, Hanover, Germany
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  • Katarina Sedej
    Affiliations
    Unit Siska, Community Health Centre Ljubljana, Ljubljana, Slovenia
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  • Barbara Jenko Bizjan
    Affiliations
    Clinical Institute of Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
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  • Katarina Trebusak Podkrajsek
    Affiliations
    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Clinical Institute of Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
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  • Thomas Danne
    Affiliations
    Children’s Hospital Auf der Bult, Janusz-Korczak-Allee, Hanover, Germany
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  • Tadej Battelino
    Affiliations
    Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia

    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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  • Urh Groselj
    Correspondence
    Correspondence and requests for materials should be addressed to Urh Groselj, University Children's Hospital, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia
    Affiliations
    Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia

    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA
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Published:August 01, 2022DOI:https://doi.org/10.1016/j.gim.2022.06.010

      Abstract

      Purpose

      In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation.

      Methods

      We analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents.

      Results

      A total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child–parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472).

      Conclusion

      Universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.

      Graphical abstract

      Keywords

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