title: 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 lacking.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia; Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia.
authors.forename: Gašper
authors.initials: G
authors.lastname: Klančar
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia.
authors.forename: Urh
authors.initials: U
authors.lastname: Grošelj
authors.affiliation: Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Kovač
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Bratanič
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Bratina
authors.affiliation: Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebušak Podkrajšek
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia; Department of Pediatrics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. Electronic address: tadej.battelino@mf.uni-lj.si.
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D017524:Slovenia / Q000453:epidemiology
keywords: cholesterol; familial hypercholesterolemia; next-generation sequencing; universal screening