Background and aims: Familial hypercholesterolemia (FH) is arguably the most common monogenic disorder in humans, but severely under-diagnosed. Individuals with untreated FH have an over 10-fold elevated risk of cardiovascular complications as compared to unaffected individuals; early diagnosis and timely management substantially reduce this risk. Slovenia has gradually implemented the program of universal FH screening in pre-school children, consisting of a two step approach: (1) universal hypercholesterolemia screening in pre-school children at the primary care level; (2) genetic FH screening in children referred to the tertiary care level according to clinical guidelines (with additional cascade screening of family members). The program is presented in detail.
Methods: We analyzed retrospective data (2012-2016), to assess the efficiency of the universal FH screening program. In that period, 280 children (59.3% female) were referred to our center through the program for having TC > 6 mmol/L (231.7 mg/dL) or >5 mmol/L (193.1 mg/dL), with a positive family history of premature cardiovascular complications at the universal hypercholesterolemia screening.
Results: 170 (57.1% female) of them were fully genotyped, 44.7% had an FH disease-causing variant (28.8% in LDLR gene, 15.9% in APOB, none in PCSK9), one patient was LIPA positive, and 40.9% of the remaining patients carried an ApoE4 isoform; genetic analysis is still ongoing for one-third of the referred patients. For almost every child with confirmed FH, one parent had highly probable FH.
Conclusions: FH was confirmed in almost half of the referred children, detected through the universal screening for hypercholesterolemia.
Keywords: APOB; Cascade screening; Children; Cholesterol; FH; Familial hypercholesterolemia; Genotype; Hypercholesterolemia; LDLR; Next-generation sequencing; PCSK9; Universal screening.
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