Homozygous familial hypercholesterolemia in a young woman with dual gene mutations of low-density lipoprotein-receptor and proprotein convertase subtilisin/kexin type 9

Abstract A 28-year old woman with a rare combination of homozygous LDLR and heterozygous PCSK9 mutations had a phenotype consistent with homozygous familial hypercholesterolemia (HoFH). She reported a clinical history of coronary and extracoronary atherosclerosis treated with three coronary stenting procedures, one coronary bypass, and aortic and mitral valve replacements. Since the patient refused lipoprotein apheresis, lipid lowering therapy with statins, ezetimibe and evolocumab was started. The desired low-density lipoprotein cholesterol (LDL-C) target was not achieved. Dose-escalated lomitapide therapy (up to 30 mg/day) was added, enabling achievement of LDL-C levels of 45 mg/dL during 24 months’ follow-up. During this period, no cardiovascular events or clinical evidence of side effects occurred. In this case, lomitapide has been used in combination with maximum-tolerated statin therapy in order to successfully treat a patient with a rare combination of mutations in both LDLR and PCSK9 genes.