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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| Published in: | Journal of the American College of Cardiology Vol. 66; no. 11; pp. 1250 - 1257 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
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15.09.2015
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| ISSN: | 1558-3597 |
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| Abstract | 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. |
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| AbstractList | BACKGROUNDIndividuals 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.OBJECTIVESThis 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.METHODSSlovenian 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.RESULTSOf 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.CONCLUSIONSMost 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. 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. |
| Author | Battelino, Tadej Klančar, Gašper Grošelj, Urh Kovač, Jernej Bratina, Nataša Bratanič, Nevenka Trebušak Podkrajšek, Katarina |
| Author_xml | – sequence: 1 givenname: Gašper surname: Klančar fullname: Klančar, Gašper organization: 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 – sequence: 2 givenname: Urh surname: Grošelj fullname: Grošelj, Urh organization: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia – sequence: 3 givenname: Jernej surname: Kovač fullname: Kovač, Jernej organization: Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia – sequence: 4 givenname: Nevenka surname: Bratanič fullname: Bratanič, Nevenka organization: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia – sequence: 5 givenname: Nataša surname: Bratina fullname: Bratina, Nataša organization: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia – sequence: 6 givenname: Katarina surname: Trebušak Podkrajšek fullname: Trebušak Podkrajšek, Katarina organization: Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC Ljubljana, Ljubljana, Slovenia; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia – sequence: 7 givenname: Tadej surname: Battelino fullname: Battelino, Tadej email: tadej.battelino@mf.uni-lj.si organization: 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 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26361156$$D View this record in MEDLINE/PubMed |
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| Keywords | cholesterol next-generation sequencing universal screening familial hypercholesterolemia |
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| Snippet | Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those... BACKGROUNDIndividuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared... |
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| SubjectTerms | Child Child, Preschool Female Humans Hyperlipoproteinemia Type II - diagnosis Hyperlipoproteinemia Type II - epidemiology Hyperlipoproteinemia Type II - genetics Male Mass Screening - methods Slovenia - epidemiology |
| Title | Universal Screening for Familial Hypercholesterolemia in Children |
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