Sheftel Alex D, Richardson Des R, Prchal Josef, Ponka Prem
Institut fur Zytobiologie, Philipps-Universitat-Marburg, Marburg, Deutschland.
Acta Haematol. 2009;122(2-3):120-33. doi: 10.1159/000243796. Epub 2009 Nov 10.
Sideroblastic anemias are a heterogeneous group of disorders, characterized by mitochondrial iron overload in developing red blood cells. The unifying characteristic of all sideroblastic anemias is the ring sideroblast, which is a pathological erythroid precursor containing excessive deposits of non-heme iron in mitochondria with perinuclear distribution creating a ring appearance. Sideroblastic anemias may be hereditary or acquired. Hereditary sideroblastic anemias are caused by defects in genes present on the X chromosome (mutations in the ALAS2, ABCB7, or GRLX5 gene), genes on autosomal chromosomes, or mitochondrial genes. Acquired sideroblastic anemias are either primary (refractory anemia with ring sideroblasts, RARS, representing one subtype of the myelodysplastic syndrome) or secondary due to some drugs, toxins, copper deficiency, or chronic neoplastic disease. The pathogenesis of mitochondrial iron loading in developing erythroblasts is diverse. Ring sideroblasts can develop as a result of a heme synthesis defect in erythroblasts (ALAS2 mutations), a defect in iron-sulfur cluster assembly, iron-sulfur protein precursor release from mitochondria (ABCB7 mutations), or by a defect in intracellular iron metabolism in erythroid cells (e.g. RARS).
铁粒幼细胞性贫血是一组异质性疾病，其特征是发育中的红细胞出现线粒体铁过载。所有铁粒幼细胞性贫血的共同特征是环形铁粒幼细胞，它是一种病理性红系前体细胞，线粒体中含有过多的非血红素铁沉积，呈核周分布，形成环形外观。铁粒幼细胞性贫血可分为遗传性或获得性。遗传性铁粒幼细胞性贫血是由X染色体上的基因缺陷（ALAS2、ABCB7或GRLX5基因突变）、常染色体上的基因或线粒体基因缺陷引起的。获得性铁粒幼细胞性贫血要么是原发性的（环形铁粒幼细胞性难治性贫血，RARS，是骨髓增生异常综合征的一种亚型），要么是由某些药物、毒素、铜缺乏或慢性肿瘤性疾病引起的继发性贫血。发育中的成红细胞线粒体铁负荷的发病机制是多样的。环形铁粒幼细胞可因成红细胞血红素合成缺陷（ALAS2突变）、铁硫簇组装缺陷、线粒体中铁硫蛋白前体释放缺陷（ABCB7突变）或红系细胞内铁代谢缺陷（如RARS）而形成。
