Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
Free Radic Biol Med. 2019 Mar;133:179-185. doi: 10.1016/j.freeradbiomed.2018.08.008. Epub 2018 Aug 8.
Sideroblastic anemia is a heterogeneous congenital and acquired disorder characterized by anemia and the presence of ring sideroblasts in the bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes involved in the heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis, and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. To date, a remarkable number of genetically undefined CSA cases remain, but a recent application of the next-generation sequencing technology has recognized novel causative genes for CSA. However, in most instances, the detailed molecular mechanisms of how defects of each gene result in the abnormal mitochondrial iron accumulation remain unclear. This review aims to cover the current understanding of the molecular pathophysiology of CSA.
铁幼粒细胞性难治性贫血是一种异质性的先天性和获得性疾病，其特征为贫血和骨髓中出现环形铁幼粒细胞。先天性铁幼粒细胞性贫血（CSA）是一种由涉及血红素生物合成、铁-硫 [Fe-S] 簇生物合成和线粒体蛋白合成的基因的突变引起的罕见疾病。最常见的 CSA 形式是 X 连锁铁幼粒细胞性贫血，由红细胞特异性 δ-氨基乙酰丙酸合酶（ALAS2）的突变引起，该酶是红细胞中血红素生物合成途径的第一个酶。迄今为止，仍有大量未明确遗传原因的 CSA 病例，但最近应用下一代测序技术已确定 CSA 的新的致病基因。然而，在大多数情况下，每个基因缺陷如何导致异常线粒体铁积累的详细分子机制仍不清楚。本综述旨在涵盖对 CSA 的分子病理生理学的当前理解。
