PDF(Pubmed)
Abstract：
UNASSIGNED: Sitosterolemia is a rare autosomal recessive genetic disorder in which patients develop hypercholesterolemia and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in the intestinal hyperabsorption of all sterols, including cholesterol and, more specifically, plant sterols or xenosterols, as well as in the impaired ability to excrete xenosterols into the bile. It remains unknown how and why some patients develop hematologic abnormalities. Only a few unrelated patients with hematologic abnormalities at the time of diagnosis have been reported. Here, we report on 2 unrelated pedigrees who were believed to have chronic immune thrombocytopenia as their most prominent feature. Both consanguineous families showed recessive gene variants in ABCG5, which were associated with the disease by in silico protein structure analysis and clinical segregation. Hepatosplenomegaly was absent. Thrombopoietin levels and megakaryocyte numbers in the bone marrow were normal. Metabolic analysis confirmed the presence of strongly elevated plasma levels of xenosterols. Potential platelet proteomic aberrations were longitudinally assessed following dietary restrictions combined with administration of the sterol absorption inhibitor ezetimibe. No significant effects on platelet protein content before and after the onset of treatment were demonstrated. Although we cannot exclude that lipotoxicity has a direct and platelet-specific impact in patients with sitosterolemia, our data suggest that thrombocytopenia is neither caused by a lack of megakaryocytes nor driven by proteomic aberrations in the platelets themselves.
摘要：
谷甾醇血症是一种罕见的常染色体隐性遗传疾病，患者会出现高胆固醇血症，并可能表现出异常的血液学和/或肝脏检查结果。在这种疾病中,ABCG5或ABCG8的功能障碍导致所有固醇的肠道过度吸收，包括胆固醇,更具体地说,植物甾醇或异种甾醇，以及分泌异种甾醇到胆汁中的能力受损。尚不清楚某些患者如何以及为什么会出现血液学异常。仅报道了少数在诊断时出现血液学异常的无关患者。这里,我们报道了2个无关的家系,这些家系认为慢性免疫性血小板减少症是其最突出的特征.两个近亲家族均在ABCG5中显示出隐性基因变异，通过蛋白质结构分析和临床分离与该疾病相关。无肝脾肿大。骨髓中血小板生成素水平和巨核细胞数量正常。代谢分析证实存在显著升高的异种甾醇血浆水平。在饮食限制和固醇吸收抑制剂依泽替米贝的施用后，纵向评估了潜在的血小板蛋白质组畸变。在治疗开始之前和之后对血小板蛋白含量没有显着影响。虽然我们不能排除脂毒性对谷甾醇血症患者有直接和血小板特异性的影响，我们的数据表明,血小板减少既不是由巨核细胞缺乏引起的,也不是由血小板自身的蛋白质组畸变引起的.
