Related Experiment Video
Updated: Apr 4, 2026
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Universal Screening for Familial Hypercholesterolemia in Children
Gašper Klančar1, Urh Grošelj2, Jernej Kovač3
1Department 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.
Insights
Familial hypercholesterolemia (FH) is genetically confirmed in most children identified through national cholesterol screening. Family history alone is insufficient for accurate FH identification, highlighting the need for genetic testing in screening programs.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Pediatrics
Background:
- Familial hypercholesterolemia (FH) significantly elevates cardiovascular risk in untreated individuals.
- Limited data exists on identifying FH through universal childhood cholesterol screening.
Purpose of the Study:
- To genetically identify FH in children with elevated cholesterol detected via national screening.
- To evaluate the effectiveness of universal screening for FH detection.
Main Methods:
- Genotyping for LDLR, PCSK9, APOB, and APOE variants in 272 Slovenian children with elevated total cholesterol (TC) and/or family history.
- Children were identified through a national universal cholesterol screening program.
Main Results:
- 57% of referred children had disease-causing FH variants (38.6% in LDLR, 18.4% in APOB).
- Nine novel variants were identified (8 in LDLR, 1 in APOB).
- The estimated FH detection rate in the screening program ranged from 53.6% to 96.3% between 2009-2013.
Conclusions:
- The majority of children referred from universal screening had genetically confirmed FH.
- Relying solely on family history may be inadequate for identifying FH patients in selective and cascade screening approaches.
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.
Related Concept Videos
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
02:46Genetic Screens
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
01:18Lipids: Dietary Sources and Requirements
01:29Pharmacogenomics: Identification of New Drug Targets
01:25Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...