Universal Screening for Familial Hypercholesterolemia in Children

Abstract Background Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those who are unaffected. Data for identification of FH with a universal screening for hypercholesterolemia in children are lacki...

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Published in:Journal of the American College of Cardiology 2015-09, Vol.66 (11), p.1250-1257
Main Authors: Klančar, Gašper, BSc, Grošelj, Urh, MD, Kovač, Jernej, PhD, Bratanič, Nevenka, MD, Bratina, Nataša, MD, Trebušak Podkrajšek, Katarina, PhD, Battelino, Tadej, MD
Format: Article
Language:English
Subjects:
Apolipoproteins
Body mass index
Cardiology
Cardiovascular
Child
Child, Preschool
Cholesterol
Colleges & universities
Deoxyribonucleic acid
DNA
familial hypercholesterolemia
Families & family life
Family medical history
Female
Genes
Heart attacks
Humans
Hyperlipoproteinemia Type II - diagnosis
Hyperlipoproteinemia Type II - epidemiology
Hyperlipoproteinemia Type II - genetics
Internal Medicine
Male
Mass Screening - methods
next-generation sequencing
Pediatrics
Population
Slovenia - epidemiology
universal screening
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Summary:Abstract Background Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those who are unaffected. Data for identification of FH with a universal screening for hypercholesterolemia in children are lacking. Objectives This study sought genetic identification of FH from a cohort of children with elevated serum total cholesterol (TC) concentration, detected in a national universal screening for hypercholesterolemia. Methods Slovenian children born between 1989 and 2009 (n = 272) with TC >6 mmol/l (231.7 mg/dl) or >5 mmol/l (193.1 mg/dl) plus a family history positive for premature cardiovascular complications, identified in a national universal screening for hypercholesterolemia at 5 years of age were genotyped for variants in LDLR , PCSK9 , APOB , and APOE. Results Of the referred children, 57.0% carried disease-causing variants for FH: 38.6% in LDLR , 18.4% in APOB , and none in PCSK9 . Nine novel disease-causing variants were identified, 8 in LDLR , and 1 in APOB . Of the remaining participants, 43.6% carried the APOE E4 isoform. Estimated detection rate of FH in the universal screening program from 2009 to 2013 was 53.6% (95% confidence interval [CI]: 34.5% to 72.8%), peaking in 2013 with an upper estimated detection rate of 96.3%. Variants in LDLR , APOB , or the APOE E4 isoform occurred in 48.6%, 60.0%, and 76.5%, respectively, of patients with a family history negative for cardiovascular complications. Conclusions Most participants who were referred from a national database of universal screening results for hypercholesterolemia had genetically confirmed FH. Data for family history may not suffice for reliable identification of patients through selective and cascade screening.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2015.07.017