1. Presence of a familial hypercholesterolemia mutation without elevated total cholesterol levels is insufficient to make diagnosis of familial hypercholesterolemia.
Evidence Rating Level: 3 (Average)
Study Rundown: Population-based child-parent screening for familial hypercholesterolemia involves testing the pediatric patient first, then the parents if the former results with a positive screen. Adults diagnosed with familial hypercholesterolemia have a significantly increased risk of coronary heart disease. In this cross-sectional study, researchers evaluated the efficacy and feasibility of screening for hypercholesterolemia in children 1-2 years of age during primary care visits. Their data demonstrated a prevalence of familial hypercholesterolemia in approximately 1/270 children, a number nearly double what is generally reported in existing literature. They estimated that for every 1000 children screened, 8 patients (4 children, 4 adults) had a positive screen for familial hypercholesterolemia. They also found that a portion of children had familial hypercholesterolemia mutations, but normal cholesterol levels.
In-Depth [cross-sectional study]: In this cross-sectional study, 10 095 children aged 1-2 years old had total cholesterol testing (including HDL and triglyceride levels) as well as genetic testing for 48 common familial hypercholesterolemia mutations (FH48) between March 2012 and 2015 across 92 general practices in the UK. The authors estimated, based off data from a previous analysis, that the total cholesterol cutoff value of 1.53 multiples of the median (MoM) that corresponded to the 99th percentile for cholesterol, would allow for detection of at least 88% of children with familial hypercholesterolemia. Children with a cholesterol level of ≥1.53 MoM who also had a FH48 mutation or a repeat 3 month cholesterol level ≥1.53 MoM were considered to have a positive screen. The parents of these children were considered to have positive screens if they had the same mutation as the child. The cholesterol level was ≥1.53 MoM in 92 children. Of these 92 children, 28 had a positive screen for familial hypercholesterolemia (0.3% of the 10 095; 95%CI 0.2-0.4) – 20 of whom had an FH48 mutation and 8 of whom had an elevated repeat cholesterol level. About 10 003 (98%) children had cholesterol levels <1.53 MoM, with 17 having an FH48 mutation. Overall, 37/10 095 children or 1/273 (95%CI 1/198-1/388), had an FH48 mutation, 32 of them had parents with FH48 mutation. Of these 32 parents, 27 pairs had elevated cholesterol in the parent with the FH48 mutation.
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