Familial hypercholesterolemia disorder in two generations simultaneously." "The use of total cholesterol alone may best discriminate between people with and without FH between the ages of 1 to 9 years." Screening of toddlers has been suggested, and results of a trial on 10,000 one-year-olds were published in 2016. Work was needed to find whether screening was cost-effective, and acceptable to families. FH is usually treated with statins. Statins act by inhibiting the enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in the liver. In response, the liver produces more LDL receptors, which remove circulating LDL from the blood. Statins effectively lower cholesterol and LDL levels,
Discovery and development of statins is needed for normal cell function and inhibition in non-hepatic cells could possibly be harmful. The essential structural components of all statins are a dihydroxyheptanoic acid unit and a ring system with different substituents. The statin pharmacophore is modified hydroxyglutaric acid component, which is structurally similar to the endogenous substrate HMG CoA and the mevaldyl CoA transition state intermediate (Figure 1). The statin pharmacophore binds to the same active site as the substrate HMG-CoA and inhibits the HMGR enzyme. It has also been shown that the HMGR is stereoselective and as a result all statins need to have the required