Hereditary sideroblastic anemia: pathophysiology and gene mutations
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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.
- Furuyama K, Kaneko K, Vargas PD. Heme as a magnificent molecule with multiple missions: heme determines its own fate and governs cellular homeostasis. Tohoku J Exp Med. 2007;213:1–16. CrossRef
- Bergmann AK, Campagne DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer. 2010;54:271–8.
- Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, et al. The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. PLoS One. 2008;3:e1970.5.
- Wulfert M, Kupper AC, Tapprich C, Bottomley SS, Bowen D, Germing U, et al. Analysis of mitochondrial DNA in 104 patients with myelodysplastic syndrome. Exp Hematol. 2008;36:577–86. CrossRef
- Cotter PD, Baumann M, Bishop DF. Enzymatic defect in “X-linked” sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. Proc Natl Acad Sci USA. 1992;89:4028–32. CrossRef
- Furuyama K, Harigae H, Kinoshita C, Shimada T, Miyaoka K, Kanda C, et al. Late-onset X-linked sideroblastic anemia following hemodialysis. Blood. 2003;101:4623–4. CrossRef
- Nakajima O, Takahashi S, Harigae H, Furuyama K, Hayashi N, Sassa S, et al. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J. 1999;22:6282–9. CrossRef
- Harigae H, Nakajima O, Suwabe N, Yokoyama H, Furuyama K, Sasaki T, et al. Aberrant iron accumulation and oxidized status of erythroid-specific δ-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts. Blood. 2003;101:1188–93. CrossRef
- Camaschella C, Campanella A, De Falco L, Boschetto L, Merlini R, Silvestri L, et al. The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood. 2007;110:1353–8. CrossRef
- Allikmets R, Raskind WH, Hutchinson A, Schueck ND, Dean M, Koeller DM. Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum Mol Genet. 1999;8:743–9. CrossRef
- Guernsey DL, Jiang H, Campagna DR, Evans SC, Ferguson M, Kellogg MD, et al. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet. 2009;41:651–3. CrossRef
- Pearson HA, Lobel JS, Kocoshis SA, Naiman JL, Windmiller J, Lammi AT, et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr. 1979;95:976–84. CrossRef
- Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, et al. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat Genet. 1999;22:300–4. CrossRef
- Inbal A, Avissar N, Shaklai M, Kuritzky A, Schejter A, Ben-David E, et al. myopathy, lactic acidosis, and sideroblastic anemia: a new syndrome. Am J Med Genet. 1995;55:372–8.
- Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am J Hum Genet. 2004;74:1303–8.
- Hereditary sideroblastic anemia: pathophysiology and gene mutations
International Journal of Hematology
Volume 92, Issue 3 , pp 425-431
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- Springer Japan
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- Sideroblastic anemia
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- 1. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
- 2. Department of Molecular Biology and Applied Physiology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan