Use

Familial hypercholesterolemia (FH) is an inherited disease and is the most common of the monogenic dyslipidemias. The prevalence of heterozygous FH is estimated at 1:250 in the U.S. population, making it the most common morbid monogenic disorder. Despite this, it is estimated that fewer than 10% of those living with FH have been diagnosed. Early childhood diagnosis is imperative due to the eventual onset of premature CVD shortening the lifespan of the affected individual. FH is characterized by very high cholesterol and LDL levels with 80% of patients expressing genetic mutations. Xanthomas or arcus cornealis may occur in patients due to abnormal lipid deposition in body tissues. Diagnosis of probable FH may be determined by lipid test results, clinical presentation or genetic testing. This test uses the Simon Broome lipid criteria for the diagnosis of FH to determine if the total cholesterol and/or the LDL cholesterol test results exceed specific cutpoints, depending upon age. If suspicion of FH is present, genetic testing may be considered. Genetic testing for FH has been recommended by many key professional societies including the American College of Cardiology, American Heart Association and National Lipid Association. The American Academy of Pediatrics (AAP) also recommends that in a clinical setting of FH suspicion, or family history, children should be offered genetic testing for diagnosis as genetic testing for FH has a 95% diagnostic yield in children. The AAP also recommends universal lipid screening for all children 9 to 11 years of age for early detection of FH. Aggressive pharmacologic treatment is usually undertaken beginning as early as 8-10 years of age upon diagnosis. There are several genetic pathogenic alterations responsible for the defects in LDL metabolism in FH. Mutations in the LDL receptor gene (LDLR) are most common, accounting for >90% of all genetic variants, whereas the apolipoprotein B (ApoB) gene and the protein convertase subtilisin/kexin type 9 (PCSK9) gene account for 5-10% and <1%, respectively. Genetic testing for FH has been recommended by many key professional societies including the American College of Cardiology, American Heart Association, and the National Lipid Association.