Iron storage disease: Facts, fiction and progress
Iron storage disease: Facts, fiction and progress
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DOI：
10.1016/j.bcmd.2007.03.009
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发表时间：
2007-09-01
影响因子：
2.3
通讯作者：
Beutler, Emest
中科院分区：
文献类型：
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作者：
Beutler, Emest
有许多形式的铁储存疾病，一些遗传性和一些获得性。最常见的遗传形式是HFE相关的血色病，这种疾病是这种表现的主要焦点。人体铁含量是通过控制吸收来调节的，过去十年的研究已经部分阐明了这种调节是如何发挥作用的。铁调素是一种由25个氨基酸组成的肽，可被铁和炎症上调，它通过与铁转运蛋白ferroportin结合并引起其降解，抑制铁吸收并将铁捕获在巨噬细胞中。大多数形式的血色素沉着症是由铁调素的失调或铁调素或铁转运蛋白本身的缺陷引起的。遗传性血色素沉着症曾经被认为是非常罕见的，但在20世纪70年代和80年代，随着更好的诊断测试的引入，它被认为是欧洲人中最常见的疾病。然而，在过去十年中进行的受控流行病学研究表明，这种疾病本身实际上是罕见的，只有其基因型和相关的生化变化才是常见的。我们不明白为什么只有少数纯合子发展成严重的疾病。现在看来，不太可能存在重要的修饰基因，尽管已知酒精有一定的影响，但过量饮酒在决定血色病表型方面可能只起了适度的作用。遗传性血色病很容易通过放血治疗。继发性疾病需要螯合治疗，最近引入有效的口服螯合剂是治疗铁过载通常被证明是致命的疾病患者的重要一步，如地中海贫血，骨髓增生异常性贫血和红细胞生成不良性贫血。虽然在过去十年中已经了解了很多关于铁稳态的调节，许多未解之谜仍然存在，这些挑战将使我们在未来数年内不得不面对。(C)2007年爱思唯尔公司All rights reserved.
There are many forms of iron storage disease, some hereditary and some acquired. The most common of the hereditary forms is HFE-associated hemochromatosis, and it is this disorder that is the main focus of this presentation. The body iron content is regulated by controlling absorption, and studies in the past decade have clarified, in part, how this regulation functions. A 25-amino-acid peptide hepcidin is up-regulated by iron and by inflammation, and it inhibits iron absorption and traps iron in macrophages by binding to and causing degradation of the iron transport protein ferroportin. Most forms of hemochromatosis results from dysregulation of hepcidin or defects of hepcidin or ferroportin themselves.Hereditary hemochromatosis was once considered to be very rare, but in the 1970s and 1980s, with the introduction of better diagnostic tests, it was considered the most common disease among Europeans. Controlled epidemiologic studies carried out in the last decade have shown, however, the disease itself actually is rare, and only its genotype and associated biochemical changes that are common. We do not understand why only a few homozygotes develop severe disease. It now seems unlikely that there are important modifying genes, and although alcohol is known to have some effect, excess drinking probably plays only a modest role in determining the hemochromatosis phenotype.Hereditary hemochromatosis is readily treated by phlebotomy. Secondary forms of the disease require chelation therapy, and the recent introduction of effective oral chelating agents is an important step forward in treating patients with disorders in which iron overload often proves to be fatal, such as thalassemia, myelodysplastic anemias, and dyserythropoietic anemias.While much has been learned about the regulation of iron homeostasis in the past decade, many mysteries remain and represent challenges that will keep us occupied for years to come. (C) 2007 Elsevier Inc. All rights reserved.