A Novel Mutation of APOB in Two Siblings with Hypercholesterolemia




Hamilton, Luke
Sprunger, Abigail
Hamby, Tyler
Wilson, Don


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A Novel Mutation of APOB in Two Siblings with Hypercholesterolemia 1 Abigail Sprunger, BS; 2L. Hamilton, MS; 3T. Hamby, PhD; and 2D. P. Wilson, MD, FNLA 1University of North Texas Health Science Center, Ft Worth, TX, and the Departments of 2Pediatric Endocrinology and Diabetes and 3Research Administration, Cook Children’s Medical Center, Ft Worth, TX, USA. Abstract Background: Familial hypercholesterolemia (FH) is a common genetic disorder cause of premature atherosclerosis due to chronically elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. Individuals with FH experience an increased risk of premature cardiovascular disease (CVD), and lack of early identification and treatment increases the risk of CVD-related coronary events later in life. We report two siblings with FH caused by a novel mutation in APOB. Methods: Electronic medical records were reviewed for two patients with FH. Case Information: Two biologically related siblings (male age 9, female age 11) were found to have LDL-C levels [greater than] 95th centile for respective age and gender. Neither sibling had preexisting medical conditions nor a history of chronic medications. Both siblings were found to have the same missense variant in the APOB gene, a novel mutation causing hypercholesterolemia. Because of parental concerns regarding use of statins, both were treated with a cholesterol absorption inhibitor. Conclusions: Despite the benefits of early identification of those at moderate-to-severe risk, several knowledge gaps impede successful cholesterol screening of children: misunderstanding goals of screening, the best screening method, and ideal age for screening and for intervention. Current guidelines recommend universal cholesterol screening and selective screening starting at 10 and 2 years of age, respectively. Although not routinely preformed, identification of a genetic mutation helps to 1) confirm the diagnosis of FH; and 2) serves as an additional risk factor for CVD, aids risk stratification and clinical-decision making, and helps determine the timing and intensity of treatment that would provide the best long-term health benefits. In addition to lipid-lowering medications, treatment should include global reduction of all CVD risk factors through health education, and adoption of life-long, heart-healthy living with a goal to reduce LDL-C levels to