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Update on Sitosterolemia and Atherosclerosis

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Abstract

Purpose of Review

The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease.

Recent Findings

Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia.

Summary

Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.

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Authors and Affiliations

  1. Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil

    Viviane Zorzanelli Rocha, Ana Paula Marte Chacra, Marcio Hiroshi Miname & Marjorie H. Mizuta

  2. Fleury Medicina E Saúde, São Paulo, SP, Brazil

    Viviane Zorzanelli Rocha

  3. Laboratory of Genetics and Molecular Cardiology (LIM13), Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil

    Mauricio Teruo Tada & Marjorie H. Mizuta

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  1. Viviane Zorzanelli Rocha
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Correspondence to Viviane Zorzanelli Rocha.

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Conflict of Interest

VZR has received honoraria from Aché, Amgen, Amryt, AstraZeneca, Biolab, Daiichi-Sankyo, GSK, Novartis, Novo Nordisk, and Sanofi.

MHM has received honoraria from Amgen.

MTT, APMC, and MHM declare no conflicts of interest.

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Rocha, V.Z., Tada, M.T., Chacra, A.P.M. et al. Update on Sitosterolemia and Atherosclerosis. Curr Atheroscler Rep 25, 181–187 (2023). https://doi.org/10.1007/s11883-023-01092-4

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