Peer-reviewed article

Towards a suitable biomarker for childhood screening for familial hypercholesterolemia: a systematic literature review.

de Kleijne VH, Hutten BA, Boelen A, Bosch AM, Corpeleijn WE et al. · 9 Oct 2026

Abstract

Familial hypercholesterolemia (FH) is a common genetic disorder causing elevated low-density lipoprotein cholesterol (LDL-c) concentrations from birth, resulting in a high risk of premature cardiovascular disease. Despite effective early treatment, FH remains underdiagnosed in children, highlighting the need for universal screening. This systematic review aims to evaluate the available evidence regarding suitable biomarkers for the purpose of universal screening for FH in childhood. The electronic databases Medline and Embase were systematically searched for studies comparing blood biomarkers in children with heterozygous FH and non-FH children. Of the 2,488 studies found, 35 were included. Although the data were constrained by considerable heterogeneity, LDL-c, total cholesterol (TC), and apolipoprotein B (ApoB) concentrations were consistently higher in children with FH across the included studies. Furthermore, increased non-high-density lipoprotein cholesterol (non-HDL-c), lathosterol, sitosterol and TC/HDL-c ratio, and a decreased squalene/TC ratio were found in children with FH. Only three screening studies combined biomarker (LDL-c, non-HDL-c and TC) and genetic testing simultaneously, revealing however limited sensitivity and specificity of these markers for FH screening in children. In this review, several biomarkers for FH screening in children were evaluated. As sensitivity and specificity data were generally not available or suboptimal, additional studies are needed to evaluate the screening performance of selected biomarkers in well-defined pediatric populations of suitable age and sex distribution, using valid analytical methods, and taking into account possible confounding factors. It is only through such studies that a well-considered selection of biomarkers can be made for the purpose of childhood screening for FH.