The association between hypercholesterotemia and sitosterolemia, and report of a sitosterolemia kindred

BACKGROUND: Sitosterolemia is associated with increases in intestinal sterol absorption, low density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk. OBJECTIVE: We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case. METHODS: Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay. RESULTS: Of 207,926 subjects tested, 4.3% had LDL-C >= 190 mg/dL. Plasma beta-sitosterol concentrations >= 8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had beta-sitosterol levels >= 15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C >= 190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a beta-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (-29%) and (beta-sitosterol to 44.6 mg/L (-27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (-38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (-80% further decrease); and his P-sitosterol decreased to 14.1 mg/L (-68% further decrease). CONCLUSIONS: Our data indicate that about 4% of subjects with LDL-C concentrations >= 190 mg/dL have plasma beta-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients. (C) 2017 Published by Elsevier Inc. on behalf of National Lipid Association.