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 δ-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.