Universal Screening for Familial Hypercholesterolemia in Children

Study Questions:

Does universal screening of hypercholesterolemia assist in identifying children with familial hypercholesterolemia (FH)?


Universal national screening for elevated cholesterol is completed in Slovenian children before the age of 5 years. Screening was started in children in 1995, and expanded to the entire country by 2013. For this study, children born in Slovenia between 1989 and 2009 were included if they had a total cholesterol >6 mmol/L (321.7 mg/dl), or a total cholesterol of >6 mmol/L (231.7 mg/dl) and a family history of premature cardiovascular disease. Genotyping was completed for variants in low-density lipoprotein receptor (LDLR), PCSK9, apolipoprotein B (APOB), and apolipoprotein E (APOE).


A total of 272 children who met criteria for elevated total cholesterol were included. Of these, 5% carried disease-causing variants for FH including 38.6% in LDLR, 18.4% in APOB, and none in PCSK9. Novel variations were identified: 8 for LDLR, and 1 for APOB. In the remaining participants, 43.6% carried APOE E4 isoform. The estimated detection rate of FH in the screening program from 2009 to 2013 was 53.6% (95% confidence interval [CI], 43.5%-72.8%), peaking in 2013 with an upper estimated detection rate of 96.3%. Variants in LDLR, APOB, or APOE E4 isoform occurred in 48.6%, 60.0%, and 76.5% of patients with a negative family history.


The investigators concluded that a majority of referred children identified through a universal screening program were genetically confirmed for FH. Data from family history alone may not be sufficient to identify all children with FH.


These findings suggest that a universal screening program may improve diagnosis of FH at an early age. Reproducing this study in other countries, along with understanding the costs related to such screening, is warranted.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, CHD & Pediatrics and Arrhythmias, CHD & Pediatrics and Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia

Keywords: Apolipoproteins B, Apolipoproteins E, Child, Cholesterol, Dyslipidemias, Genotype, Hypercholesterolemia, Hyperlipoproteinemia Type II, Metabolic Syndrome X, Primary Prevention, Receptors, LDL

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