sideroblastic anemia


Summary: Anemia characterized by the presence of erythroblasts containing excessive deposits of iron in the marrow.

Top Publications

  1. Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, et al. A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia. Am J Hematol. 1999;62:112-4 pubmed synthase gene (ALAS2) was identified in a Japanese male with pyridoxine-responsive sideroblastic anemia. Activity of the mutant delta-aminolevulinate synthase protein expressed in vitro was 15...
  2. Cazzola M, Invernizzi R, Bergamaschi G, Levi S, Corsi B, Travaglino E, et al. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. 2003;101:1996-2000 pubmed
    ..cells from 13 patients with refractory anemia with ring sideroblasts (RARS) and 3 patients with X-linked sideroblastic anemia (XLSA) were analyzed for the distribution of cytoplasmic H ferritin (HF) and MtF using immunocytochemical ..
  3. Ljung T, Bäck R, Hellstrom Lindberg E. Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors. Haematologica. 2004;89:1446-53 pubmed
    ..Hence, the finding of hypochromic red cells should not routinely be interpreted as a marker for Epo-induced functional iron deficiency in MDS. ..
  4. Patton J, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel Ghodsian N. Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. J Biol Chem. 2005;280:19823-8 pubmed
    ..the PUS1 gene affecting a highly conserved amino acid has been associated with mitochondrial myopathy and sideroblastic anemia (MLASA), a rare autosomal recessive oxidative phosphorylation disorder...
  5. Rouault T, Tong W. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol. 2005;6:345-51 pubmed
    ..Recent studies in model systems and humans reveal that iron-sulphur proteins have important roles in mitochondrial iron homeostasis and in the pathogenesis of the human disease Friedreich ataxia. ..
  6. Shimada Y, Okuno S, Kawai A, Shinomiya H, Saito A, Suzuki M, et al. Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. J Hum Genet. 1998;43:115-22 pubmed
    ..1-q13.3 by fluorescence in-situ hybridization. As band Xq13 has been implicated in X-linked sideroblastic anemia with spinocerebellar ataxia, hABC7 becomes a candidate gene for this heritable disorder.
  7. 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 pubmed
    ..GLRX5 function is highly conserved, but at variance with zebrafish, its defect in humans leads to anemia and iron overload. ..
  8. Bergmann A, Campagna D, McLoughlin E, Agarwal S, Fleming M, Bottomley S, et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer. 2010;54:273-8 pubmed publisher
    ..Among the congenital sideroblastic anemias (CSAs), the most common form is X-linked sideroblastic anemia, due to mutations in 5-aminolevulinate synthase (ALAS2)...
  9. Bekri S, Kispal G, Lange H, Fitzsimons E, Tolmie J, Lill R, et al. Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood. 2000;96:3256-64 pubmed
    ..mutation in the human ABC7 gene was shown to be the defect in members of a family affected with X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A)...

More Information


  1. Ramirez J, Schaad O, Durual S, Cossali D, Docquier M, Beris P, et al. Growth differentiation factor 15 production is necessary for normal erythroid differentiation and is increased in refractory anaemia with ring-sideroblasts. Br J Haematol. 2009;144:251-62 pubmed publisher
    ..Taken together, our findings demonstrate a new role for GDF15 in normal erythropoiesis as well as in the ineffective erythropoiesis of RARS patients. ..
  2. Pondarre C, Campagna D, Antiochos B, Sikorski L, Mulhern H, Fleming M. Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood. 2007;109:3567-9 pubmed
    X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare syndromic form of inherited sideroblastic anemia associated with spinocerebellar ataxia, and is due to mutations in the mitochondrial ATP-binding cassette transporter Abcb7...
  3. Allikmets R, Raskind W, Hutchinson A, Schueck N, Dean M, Koeller D. 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 pubmed
    X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia with hypochromia and microcytosis...
  4. 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 pubmed
    Mitochondrial myopathy and sideroblastic anemia (MLASA) is a rare, autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow...
  5. Furuyama K, Sassa S. Multiple mechanisms for hereditary sideroblastic anemia. Cell Mol Biol (Noisy-le-grand). 2002;48:5-10 pubmed
    Hereditary sideroblastic anemia (HSA) is a heterogeneous group of inherited anemic disorders which is characterized by the presence of ringed sideroblasts in the bone marrow, microcytic hypochromic anemia and typically its X-linked ..
  6. Cotter P, Baumann M, Bishop D. Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. Proc Natl Acad Sci U S A. 1992;89:4028-32 pubmed
    ..identifying this gene as the logical candidate for the enzymatic defect causing "X-linked" sideroblastic anemia. To investigate this hypothesis, the 11 exonic coding regions of the delta-aminolevulinate synthase gene ..
  7. Cavadini P, Biasiotto G, Poli M, Levi S, Verardi R, Zanella I, et al. RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload. Blood. 2007;109:3552-9 pubmed
    X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells...
  8. Rouault T, Tong W. Iron-sulfur cluster biogenesis and human disease. Trends Genet. 2008;24:398-407 pubmed publisher
    ..attributable to abnormal Fe-S cluster biogenesis has extended beyond Friedreich ataxia to include a sideroblastic anemia with deficiency of glutaredoxin 5 and a myopathy associated with a deficiency of a Fe-S cluster assembly ..
  9. Cox T, Bottomley S, Wiley J, Bawden M, Matthews C, May B. X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase. N Engl J Med. 1994;330:675-9 pubmed
    X-linked sideroblastic anemia is usually associated with reduced 5-aminolevulinate synthase activity in erythroid cells, and some cases are responsive to treatment with pyridoxine, the precursor to the cofactor of the enzyme...
  10. Guernsey D, Jiang H, Campagna D, Evans S, Ferguson M, Kellogg M, et al. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet. 2009;41:651-3 pubmed publisher positional cloning, we define a previously unknown form of autosomal recessive nonsyndromic congenital sideroblastic anemia, associated with mutations in the gene encoding the erythroid specific mitochondrial carrier family protein ..
  11. Ye H, Jeong S, Ghosh M, Kovtunovych G, Silvestri L, Ortillo D, et al. Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest. 2010;120:1749-61 pubmed publisher
    ..5 (GLRX5) deficiency has previously been identified as a cause of anemia in a zebrafish model and of sideroblastic anemia in a human patient...
  12. Steensma D, Hecksel K, Porcher J, Lasho T. Candidate gene mutation analysis in idiopathic acquired sideroblastic anemia (refractory anemia with ringed sideroblasts). Leuk Res. 2007;31:623-8 pubmed
    For most cases of idiopathic acquired sideroblastic anemia (IASA), the molecular pathogenesis is unknown, despite the consistent morphological signature of abundant pathological ringed sideroblasts with their characteristic iron-engorged ..
  13. Riley L, Cooper S, Hickey P, Rudinger Thirion J, McKenzie M, Compton A, et al. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. Am J Hum Genet. 2010;87:52-9 pubmed publisher
    ..SNP-based homozygosity analysis of a family with affected members displaying myopathy, lactic acidosis, and sideroblastic anemia (MLASA). We subsequently identified the same mutation in another unrelated MLASA patient...
  14. 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 pubmed publisher
    ..We considered that the inherited X-linked sideroblastic anemia with ataxia (XLSA/A) might be informative for the acquired disorder, RARS...
  15. Maguire A, Hellier K, Hammans S, May A. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L. Br J Haematol. 2001;115:910-7 pubmed
    ..An uncle affected by ataxia also carried this mutation. This study supports the recently hypothesized involvement of the ABC7 gene in XLSA/A and highlights a protein structure region of importance to this syndrome...
  16. Camaschella C. Hereditary sideroblastic anemias: pathophysiology, diagnosis, and treatment. Semin Hematol. 2009;46:371-7 pubmed publisher
    Inherited sideroblastic anemia comprises several rare anemias due to heterogeneous genetic lesions, all characterized by the presence of ringed sideroblasts in the bone marrow...
  17. Sussman N, Lee P, Dries A, Schwartz M, Barton J. Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G. Acta Haematol. 2008;120:168-73 pubmed publisher
    X-linked sideroblastic anemia (XLSA) is associated with iron overload and mutations in ALAS2, which encodes 5-aminolevulinate synthase. There are few reports of XLSA in persons of sub-Saharan African descent...
  18. Domingo Claros A, Alonso E, Banda Ed E. Schizophrenia and refractory anaemia with ring sideroblasts. Br J Haematol. 2004;125:543 pubmed
  19. Levi S, Rovida E. The role of iron in mitochondrial function. Biochim Biophys Acta. 2009;1790:629-36 pubmed publisher
    ..Relevant updates with regard to the Fe/S cluster and heme biosynthetic pathways, as well as the relationship between mitochondrial iron homeostasis impairment and related diseases, are also discussed. ..
  20. Yoshimi A, Abdel Wahab O. Splicing factor mutations in MDS RARS and MDS/MPN-RS-T. Int J Hematol. 2017;105:720-731 pubmed publisher
    ..mechanisms of mis-splicing caused by mutant SF3B1 and the pathogenesis of RSs in the context of congenital sideroblastic anemia as well as RARS with SF3B1 mutations...
  21. Yanagihara I, Inui K, Yanagihara K, Park Y, Tanaka J, Ozono K, et al. Fluorescence in situ hybridization analysis of peripheral blood cells in Pearson marrow-pancreas syndrome. J Pediatr. 2001;139:452-5 pubmed
    ..The method demonstrated a shift in heteroplasmy, paralleling the hematologic improvement. ..
  22. Hunter G, Ferreira G. 5-aminolevulinate synthase: catalysis of the first step of heme biosynthesis. Cell Mol Biol (Noisy-le-grand). 2009;55:102-10 pubmed
    ..erythroid-specific aminolevulinate synthase gene are associated with the erythropoietic disorder X-linked sideroblastic anemia. Recent kinetic and crystallographic data have facilitated an unprecedented understanding of how this ..
  23. Navarro I, Ruiz M, Cabello A, Collado R, Ferrer R, Hueso J, et al. Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients. Leuk Res. 2006;30:971-7 pubmed
    ..The WHO classification establishes more homogeneous subcategories than the FAB classification and is also able to identify groups with different prognoses. ..
  24. Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. Br J Haematol. 2000;108:724-8 pubmed
    ..This prospective study strongly supported our conclusion that cytomorphological distinction between PSA and RARS provides valuable prognostic information. ..
  25. Beaumont C. Ferroportin in erythroid cells: a protective mechanism?. Haematologica. 2005;90:1585 pubmed
  26. Breccia M, Mengarelli A, Mancini M, Biondo F, Gentilini F, Latagliata R, et al. Myelodysplastic syndromes in patients under 50 years old: a single institution experience. Leuk Res. 2005;29:749-54 pubmed
    ..001) and high risk by IPSS score (p = 0.0003) were found to be predictive for a higher risk of transformation to AML. Presenting features in young MDS patients may identify subjects at higher risk of unfavourable outcome. ..
  27. Cazzola M, Beguin Y, Bergamaschi G, Guarnone R, Cerani P, Barella S, et al. Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis. Br J Haematol. 1999;106:752-5 pubmed
    ..Multiple regression analysis showed that 62% (P < 0.0001) of the variation in serum ferritin was explained by age and by changes in soluble TfR. ..
  28. Acha V, Zaragüeta M, Martinez Y, Cobo F. [Linezolid-induced anemia]. Enferm Infecc Microbiol Clin. 2003;21:321-2 pubmed
  29. Willis M, Monaghan S, Miller M, McKenna R, Perkins W, Levinson B, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol. 2005;123:125-31 pubmed
    Copper deficiency is a rare cause of sideroblastic anemia and neutropenia that often is not suspected clinically...
  30. Sheftel A, Richardson D, Prchal J, Ponka P. Mitochondrial iron metabolism and sideroblastic anemia. Acta Haematol. 2009;122:120-33 pubmed publisher
    ..g. rars). ..
  31. Cursiefen C, Kuchle M, Scheurlen W, Naumann G. Bilateral zonular cataract associated with the mitochondrial cytopathy of Pearson syndrome. Am J Ophthalmol. 1998;125:260-1 pubmed
    ..Mitochondrial cytopathies such as Pearson syndrome should be included in the differential diagnosis of congenital and early juvenile cataract. ..
  32. Cazzola M, Malcovati L. Diagnosis and treatment of sideroblastic anemias: from defective heme synthesis to abnormal RNA splicing. Hematology Am Soc Hematol Educ Program. 2015;2015:19-25 pubmed publisher
    ..X-linked sideroblastic anemia (XLSA) is caused by germline mutations in ALAS2...
  33. Koc S, Harris J. Sideroblastic anemias: variations on imprecision in diagnostic criteria, proposal for an extended classification of sideroblastic anemias. Am J Hematol. 1998;57:1-6 pubmed
    ..We recommend a more precise evaluation and documentation of the components that characterize the sideroblastic abnormality and propose an extended classification of the sideroblastic anemias. ..
  34. Szpurka H, Jankowska A, Makishima H, Bodo J, Bejanyan N, Hsi E, et al. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations. Leuk Res. 2010;34:969-73 pubmed publisher
    ..JAK2V617F/MPLW515L mutations were absent in TET2/ASXL1 mutants, indicating that similar clinical phenotype can be produced by various MPN-associated mutations and that additional unifying lesions may be present in RARS-T. ..
  35. Le Rouzic M, Fouquet C, Leblanc T, Touati M, Fouyssac F, Vermylen C, et al. Non syndromic childhood onset congenital sideroblastic anemia: A report of 13 patients identified with an ALAS2 or SLC25A38 mutation. Blood Cells Mol Dis. 2017;66:11-18 pubmed publisher
    The most frequent germline mutations responsible for non syndromic congenital sideroblastic anemia are identified in ALAS2 and SLC25A38 genes...
  36. Martin F, Bydlon G, Welsh M, Friedman J. A method for rapid mouse siderocyte enrichment. Exp Hematol. 2005;33:1493-9 pubmed
    ..This data will help develop our understanding of the pathogenesis of SA and other disorders characterized by iron overload. ..
  37. Almhanna K, Khan P, Schaldenbrand M, Momin F. Sideroblastic anemia after bariatric surgery. Am J Hematol. 2006;81:155-6 pubmed
  38. Pondarre C, Antiochos B, Campagna D, Clarke S, Greer E, Deck K, et al. The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum Mol Genet. 2006;15:953-64 pubmed
    ..The mitochondrial ABC half-transporter Abcb7, which is mutated in X-linked sideroblastic anemia with ataxia in humans, is a functional ortholog of yeast Atm1p and is predicted to export a mitochondrially ..
  39. Riley L, Rudinger Thirion J, Schmitz Abe K, Thorburn D, Davis R, Teo J, et al. LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure. JIMD Rep. 2016;28:49-57 pubmed
    ..The proband was born prematurely with severe lactic acidosis, hydrops, and sideroblastic anemia. She had multisystem complications with hyaline membrane disease, impaired cardiac function, a coagulopathy,..
  40. Dufay J, Fernández Murray J, McMaster C. SLC25 Family Member Genetic Interactions Identify a Role for HEM25 in Yeast Electron Transport Chain Stability. G3 (Bethesda). 2017;7:1861-1873 pubmed publisher
    ..Mutations in the human SLC25A38 gene cause congenital sideroblastic anemia. The full extent to which SLC25 family members coregulate heme synthesis with other mitochondrial functions ..
  41. Smetana K, Jirásková I, Malasková V, Cermak J. A cytochemical note on nucleoli of granulocytic precursors and granulocytes in patients suffering from the refractory anemia with excess blasts (RAEB) of the myelodysplastic syndrome (MDS). Neoplasma. 2002;49:5-9 pubmed
  42. Tehranchi R, Invernizzi R, Grandien A, Zhivotovsky B, Fadeel B, Forsblom A, et al. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood. 2005;106:247-53 pubmed
    ..In conclusion, aberrant MtF expression in RARS erythroblasts occurs at a very early stage of erythroid differentiation and is paralleled by an up-regulation of genes involved in this process. ..
  43. Ayas M, Al Jefri A, Mustafa M, Al Mahr M, Shalaby L, Solh H. Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation. Br J Haematol. 2001;113:938-9 pubmed
    ..Graft-versus-host disease (GVHD) prophylaxis was with cyclosporin A and methotrexate. All patients engrafted, and are alive and transfusion independent. SCT can be curative for patients with SA. ..
  44. Furuyama K, Uno R, Urabe A, Hayashi N, Fujita H, Kondo M, et al. R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. Br J Haematol. 1998;103:839-41 pubmed
    ..These findings suggest that the R411C mutation accounts for low ALAS activity and a partial pyridoxine-responsiveness of the disease in the patient. ..
  45. Pereira J, Gutiérrez E, Ribeiro M. Gene symbol: ALAS2. Disease: sideroblastic anaemia. Hum Genet. 2004;115:533 pubmed
  46. Lindemeyer R, Goldberg E, Pinto A. Dental management of a child with congenital sideroblastic anemia: a case report. Pediatr Dent. 2007;29:315-9 pubmed
    ..The purpose of this case report was to describe the dental management of a child with congenital sideroblastic anemia--a rare hematologic disorder--and to emphasize how important it is for pediatric dentists to be cognizant ..
  47. Martin F, Bydlon G, Friedman J. SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress. Antioxid Redox Signal. 2006;8:1217-25 pubmed
    ..mitochondrial- derived oxidants-plays an important role in the pathogenesis of the human disorder, sideroblastic anemia. Here we review the relation between mitochondrial dysfunction and sideroblastic anemia, describe several ..
  48. Schmidt Mende J, Tehranchi R, Forsblom A, Joseph B, Christensson B, Fadeel B, et al. Granulocyte colony-stimulating factor inhibits Fas-triggered apoptosis in bone marrow cells isolated from patients with refractory anemia with ringed sideroblasts. Leukemia. 2001;15:742-51 pubmed
    ..Our data support the clinical benefit of G-CSF in this subgroup of myelodysplastic syndromes. ..
  49. Alcindor T, Bridges K. Sideroblastic anaemias. Br J Haematol. 2002;116:733-43 pubmed
  50. Srinivasan V, Pierik A, Lill R. Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1. Science. 2014;343:1137-40 pubmed publisher
    ..Defects in the human ortholog ABCB7 cause the sideroblastic anemia XLSA/A...
  51. Sommerville E, Ng Y, Alston C, Dallabona C, Gilberti M, He L, et al. Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy. JAMA Neurol. 2017;74:686-694 pubmed publisher
    YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations...
  52. Knipp S, Strupp C, Gattermann N, Hildebrandt B, Schapira M, Giagounidis A, et al. Presence of peripheral blasts in refractory anemia and refractory cytopenia with multilineage dysplasia predicts an unfavourable outcome. Leuk Res. 2008;32:33-7 pubmed
    ..00005). Median survival of patients with PB was not different from that of RAEB I. We therefore propose to consider patients with PB, regardless of medullary blast, as RAEB I. ..
  53. Renneville A, Quesnel B, Charpentier A, Terriou L, Crinquette A, Lai J, et al. High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Leukemia. 2006;20:2067-70 pubmed