Finberg Karin E
Department of Pathology, Duke University Medical Center, Durham, NC.
Semin Hematol. 2009 Oct;46(4):378-86. doi: 10.1053/j.seminhematol.2009.06.006.
Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to parenteral iron therapy. IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver. IRIDA patients show inappropriately elevated levels of hepcidin, a circulating hormone produced by the liver that inhibits both iron absorption from the intestine and iron release from macrophage stores. Recent studies suggest that TMPRSS6 normally acts to downregulate hepcidin expression by cleaving hemojuvelin, a membrane-bound protein that promotes hepcidin signaling in hepatocytes. A discussion of the clinical presentation of IRIDA, the molecular genetics of this disorder, and recent studies elucidating the underlying pathophysiology are presented.
铁难治性缺铁性贫血（IRIDA）是一种常染色体隐性疾病，其特征为缺铁性贫血，对口服铁剂治疗无反应，但对胃肠外铁剂治疗有部分反应。最近研究表明，IRIDA是由TMPRSS6基因突变引起的，该基因编码一种由肝脏表达的跨膜丝氨酸蛋白酶（也称为matriptase-2）。IRIDA患者的铁调素水平异常升高，铁调素是一种由肝脏产生的循环激素，它既能抑制肠道对铁的吸收，又能抑制巨噬细胞储存铁的释放。最近的研究表明，TMPRSS6通常通过切割血色素沉着症相关蛋白发挥下调铁调素表达的作用，血色素沉着症相关蛋白是一种膜结合蛋白，可促进肝细胞中铁调素信号传导。本文将对IRIDA的临床表现、该疾病的分子遗传学以及阐明其潜在病理生理学的最新研究进行讨论。
