Familial hypercholesterolemia: clinical pearls

FH, in its commonest type, is due to an autosomal dominant defect in the genes encoding for proteins involved in LDL metabolism. There are autosomal recessive variants, but these are much less common.3 Patients can have a homozygous or a heterozygous defect, which will determine the severity of the disease and the age of onset of CV disease manifestations. The three main genetic defects that lead to FH are defects in the LDL receptor gene (most common), apolipoprotein B-100 (ApoB-100) gene4, and proprotein convertase subtilisin/Kexin type 9 (PCSK9) gene.5 These three mutations account for 60 to 80 percent of patients with definite FH.6 Other mutations, like the signaltransducing adaptor family member 1 (STAP1) gene mutation, have been reported to be associated with FH.7