Management of homozygous familial hypercholesterolaemia in two brothers

Abstract

Homozygous familial hypercholesterolaemia (HoFH) is a rare, genetic disorder of abnormally high levels of low-density lipoprotein cholesterol (LDL-C) requiring aggressive interventions to retard the evolution of atherosclerotic cardiovascular disease. We treated two brothers (ages 46 years and 47 years) with HoFH with statins, lipoproteinapheresis (LA) and the microsomal triglyceride transfer protein inhibitor lomitapide. Both brothers carried the p.Thr434Arg homozygous LDLR mutation and had childhood total cholesterol levels >700 mg/dL. Inter-LA LDL-C levels remained high; therefore, they were given escalating doses of oral lomitapide (5-10 mg/day). One brother was able to maintain LDL-C levels <70 mg/dL and stop LA. Lomitapide was well tolerated, with only an episode of headache requiring dose reduction from 40 mg/day to 20 mg/day in one patient. In two HoFH cases, lomitapide was an effective and well-tolerated adjunct therapy. Lomitapide doses required to maintain LDL-C goal levels appear to be lower in clinical practice than in clinical trials.

Keywords: congenital disorders; endocrine system; lipid disorders.

Figure 1

LDL-C values at baseline and during LDL-C apheresis with different doses of lomitapide in Patient 1. LDL-C, low-density lipoprotein cholesterol.

Figure 2

Evolution of LDL-C preapheresis, apoB preapheresis and LDL-C interapheresis values with different doses of lomitapide in patient 1. Aph, apheresis; ApoB, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol; lomitapide doses are mg/day.

Figure 3

LDL-C values at baseline and during LDL-C apheresis with different doses of lomitapide in patient 2. LDL-C, low-density lipoprotein cholesterol.

Figure 4

Evolution of LDL-C preapheresis, apoB preapheresis and LDL-C interapheresis values with different doses of lomitapide in patient 2. Aph, apheresis; ApoB, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol; lomitapide doses are mg/day.