Hereditary sideroblastic anemia: pathophysiology and gene mutations
Hereditary sideroblastic anemia: pathophysiology and gene mutations
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DOI：
10.1007/s12185-010-0688-4
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发表时间：
2010-10-01
影响因子：
2.1
通讯作者：
Furuyama, Kazumichi
中科院分区：
文献类型：
--
作者：
Harigae, Hideo;Furuyama, Kazumichi
铁粒幼细胞贫血的特征是骨髓中出现环形铁粒幼细胞的贫血。环状铁粒幼细胞是有红细胞，其特征是由于铁利用受损而导致铁在核周线粒体中积累。铁粒幼细胞贫血有两种形式，即遗传性和获得性铁粒幼细胞贫血。遗传性铁粒幼细胞贫血是一种罕见的异质性疾病，由参与血红素生物合成、铁硫 (Fe-S) 簇生物发生或 Fe-S 簇转运和线粒体代谢的基因突变引起。最常见的遗传性铁粒幼细胞贫血是 X 连锁铁粒幼细胞贫血 (XLSA)，由红系特异性 δ-氨基乙酰丙酸合酶基因 (ALAS2) 突变引起，ALAS2 是红系细胞中血红素生物合成的第一个酶。由线粒体转运蛋白 SLC25A38 基因突变引起的铁粒幼细胞贫血是第二常见的遗传性铁粒幼细胞贫血。其他形式的遗传性铁粒幼细胞贫血非常罕见，并且伴随着造血组织以外的器官功能受损，例如由于线粒体代谢受损而导致的神经系统、肌肉或外分泌腺。此外，仍有大量病例患有基因未明确的遗传性铁粒幼细胞贫血。对这些病例的分子分析不仅有助于开发有效的治疗方法，而且有助于了解线粒体铁代谢。
Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. Inherited sideroblastic anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or Fe-S cluster transport, and mitochondrial metabolism. The most common inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA) caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited sideroblastic anemia. Other forms of inherited sideroblastic anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited sideroblastic anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.