Genetic basis and hematologic manifestations of sitosterolemia in a group of Turkish patients

Abstract

BACKGROUND: Sitosterolemia is a rare lipid disorder caused by mutations in adenosine triphosphatebinding cassette genes ( ABCG ) 5 and 8. OBJECTIVE: To evaluate the phenotypic/genotypic features of sitosterolemia in a group of Turkish patients. METHODS: Seven probands with unexplained hematologic abnormalities and their 13 relatives were enrolled. Sterol levels were measured by gas chromatography and genetic studies were performed using Sanger sequencing. Individuals were diagnosed with sitosterolemia if they were found to have frankly elevated sitosterol level > 15 mu g/mL and/or pathogenic variants of the ABCG 5/ ABCG 8. RESULTS: The seven probands and their six relatives were diagnosed with frank sitosterolemia, and all these patients had hematologic abnormalities. The remaining seven relatives were asymptomatic heterozygous carriers. Three novel variants in the ABCG 5 gene (c.161G > A , c.1375C > T , IVS10-1G > T ), one novel variant in the ABCG 8 gene (c.1762G > C ) and one known variant in the ABCG 5 gene (c.1336 C > T ) were identified. No variant was identified in one case. The mean sitosterol level was significantly higher and mean platelet count was significantly lower in patients with homozygous variants compared to heterozygous variants ( p < 0.05, for all). Diets low in plant sterols were recommended for 13 symptomatic cases. Four homozygotes received ezetimibe, and their splenomegaly, anemia, and thrombocytopenia completely resolved except one. CONCLUSION: The five pathogenic variants identified in this study indicate the genetic heterogeneity of sitosterolemia in Turkish population. Patients with unexplained hematologic abnormalities (specifically macrothrombocytopenia) should have their sterol level measured as initial testing. Ezetimibe can be a good choice for sitosterolemia. (c) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.