Management of Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a devastating codominant autosomal disease mostly caused by loss off function variants affecting the LDL receptor gene (LDLR) and is characterized by extremely elevated plasma LDL-cholesterol (LDL-C), diffuse cutaneous and tendinous xanthomas, corneal arcus, and early diffuse atherosclerotic cardiovascular disease (ASCVD). In addition, HoFH individuals usually develop severe aortic valve or supra-aortic valve diseases. HoFH is usually refractory to standard pharmacological lipid-lowering therapies and use of other medications like PCSK9 inhibitors, microsomal transfer protein inhibitors, and lipoprotein apheresis (LA) are necessary. Lipid-lowering therapy has increased ASCVD event-free survival from the second to the third decade of life in HoFH individuals; however, coronary atherosclerosis and aortic valve or supra-aortic valve disease still cause striking early morbidity and mortality.