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. She reported a clinical history of coronary and extracoronary atherosclerosis treated with 3 coronary stenting procedures, one coronary bypass, and aortic and mitral valve replacements. Because the patient refused lipoprotein apheresis, lipid-lowering therapy with statins, ezetimibe, and evolocumab was started. The desired low-density lipoprotein cholesterol target was not achieved. Dose-escalated lomitapide therapy (up to 30 mg/d) was added, enabling achievement of low-density lipoprotein cholesterol 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 to successfully treat a patient with a rare combination of mutations in both LDLR and PCSK9 genes.

Keywords: Evolocumab; Genetics; Homozygous familial hypercholesterolemia; Lipoprotein apheresis; Lomitapide; Low-density lipoprotein receptor; Mutation; Proprotein convertase subtilisin/kexin type 9.