Rocha Viviane Zorzanelli, Tada Mauricio Teruo, Chacra Ana Paula Marte, Miname Marcio Hiroshi, Mizuta Marjorie H
Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
Fleury Medicina E Saúde, São Paulo, SP, Brazil.
Curr Atheroscler Rep. 2023 May;25(5):181-187. doi: 10.1007/s11883-023-01092-4. Epub 2023 Mar 10.
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.
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. 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.
本综述旨在总结关于谷甾醇血症的重要且最新的信息。谷甾醇血症是一种遗传性脂质紊乱疾病，其特征为血浆植物甾醇水平升高。这种甾醇蓄积病症是由ABCG5或ABCG8双等位基因功能丧失性遗传变异引起的，导致植物甾醇的肠道吸收增加和肝脏排泄减少。临床上，谷甾醇血症患者通常表现为黄瘤病、血浆胆固醇水平升高和早发性动脉粥样硬化疾病，但临床表现可能高度异质性。因此，识别这种病症需要高度怀疑，并通过基因诊断或血浆植物甾醇测量来确诊。采用植物甾醇限制饮食和肠道胆固醇吸收抑制剂依泽替米贝治疗谷甾醇血症可有效降低血浆植物甾醇水平，这是该病的一线治疗方法。
由于高胆固醇血症在谷甾醇血症患者中经常存在，对于具有家族性高胆固醇血症（FH）临床标准但FH相关基因无变异的患者，在ABCG5和ABCG8中寻找遗传变异很重要。事实上，最近的研究表明，ABCG5/ABCG8中的遗传变异可模拟FH，即使是杂合状态，它们也可能会加重严重血脂异常患者的表型。谷甾醇血症是一种遗传性脂质紊乱疾病，其特征是循环植物甾醇水平升高，临床表现为黄瘤病、血液系统疾病和早期动脉粥样硬化。认识到这种病症作为早发性动脉粥样硬化疾病的一种罕见但常被漏诊且可治疗的病因至关重要。
