Universal Screening for Familial Hypercholesterolemia in Children

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. This study sough...

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Veröffentlicht in:Journal of the American College of Cardiology Jg. 66; H. 11; S. 1250 - 1257
Hauptverfasser: Klančar, Gašper, Grošelj, Urh, Kovač, Jernej, Bratanič, Nevenka, Bratina, Nataša, Trebušak Podkrajšek, Katarina, Battelino, Tadej
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 15.09.2015
Schlagworte:
Child
Child, Preschool
Female
Humans
Hyperlipoproteinemia Type II - diagnosis
Hyperlipoproteinemia Type II - epidemiology
Hyperlipoproteinemia Type II - genetics
Male
Mass Screening - methods
Slovenia - epidemiology
Slovenia
cholesterol
next-generation sequencing
universal screening
familial hypercholesterolemia
ISSN:1558-3597
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Zusammenfassung: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. 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. 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. 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. 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1558-3597
DOI:10.1016/j.jacc.2015.07.017