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Sideroblastic Anemias: Diagnosis and Management

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Nonmalignant Hematology

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Abstract

The term sideroblastic anemia (SA) is used to define a diverse group of disorders with the common finding of ringed sideroblasts noted on bone marrow evaluations (Fig. 1). The presence of this morphology is due to iron deposition in the mitochondria of the erythroid progenitor cells. Congenital SA may be due to one of several defined gene abnormalities or due to an as yet unknown defect (Bergmann et al. 2010). Acquired SA is caused by nutritional deficits, medications, or clonal myelodysplastic disorders. While the precise incidence of congenital SA is unknown and it is likely underdiagnosed and reported, the frequency of acquired cases appears to be much greater than congenital cases.

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References

  • Aivado M, Gattermann N, Rong A, Giagounidis AA, Prall WC, Czibere A, Hildebrandt B, Haas R, Bottomley SS. X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells Mol Dis. 2006;37:40–5.

    Article  CAS  PubMed  Google Scholar 

  • Ardissone A, Lamantea E, Quartararo J, Dallabona C, Carrara F, Moroni I, Donnini C, Garavaglia B, Zeviani M, Uziel G. A novel homozygous YARS2 mutation in two Italian siblings and a review of literature. JIMD Rep. 2015;20:95–101.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gumruk F. Thiamine-responsive megaloblastic anemia syndrome. Int J Hematol. 2010;92:524–6.

    Article  PubMed  Google Scholar 

  • Bekri S, D’Hooghe M, Vermeersch P. X-linked sideroblastic anemia and ataxia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. GeneReviews(R). Seattle: University of Washington; 1993.

    Google Scholar 

  • Bergmann AK, Campagna DR, Mcloughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ. 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  PubMed Central  Google Scholar 

  • Beshlawi I, Al Zadjali S, Bashir W, Elshinawy M, Alrawas A, Wali Y. Thiamine responsive megaloblastic anemia: the puzzling phenotype. Pediatr Blood Cancer. 2014;61:528–31.

    Article  PubMed  Google Scholar 

  • Bottomley SS. Sideroblastic anemia: death from iron overload. Hosp Pract (Off Ed). 1991;26 Suppl 3:55–6.

    Article  Google Scholar 

  • Bottomley SS. Porphyria. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA, Means Jr RT, editors. Wintrobe’s clinical hematology. 12th ed. Philadelphia: Lippincott Williams & Wilkins; 2009a.

    Google Scholar 

  • Bottomley SS. Sideroblastic anemias. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA, Means Jr RT, editors. Wintrobe’s clinical hematology. 12th ed. Philadelphia: Lippincott Williams & Wilkins; 2009b.

    Google Scholar 

  • Bottomley SS, Fleming MD. Sideroblastic anemia: diagnosis and management. Hematol Oncol Clin N Am. 2014;28:653–70, v.

    Article  Google Scholar 

  • Broseus J, Florensa L, Zipperer E, Schnittger S, Malcovati L, Richebourg S, Lippert E, Cermak J, Evans J, Mounier M, Raya JM, Bailly F, Gattermann N, Haferlach T, Garand R, Allou K, Besses C, Germing U, Haferlach C, Travaglino E, Luno E, Pinan MA, Arenillas L, Rozman M, Perez Sirvent ML, Favre B, Guy J, Alonso E, Ahwij N, Jerez A, Hermouet S, Maynadie M, Cazzola M, Girodon F. Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis. Haematologica. 2012;97:1036–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broseus J, Alpermann T, Wulfert M, Florensa Brichs L, Jeromin S, Lippert E, Rozman M, Lifermann F, Grossmann V, Haferlach T, Germing U, Luno E, Girodon F, Schnittger S, MPN & EURONET, M. P. Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis. Leukemia. 2013;27:1826–31.

    Article  CAS  PubMed  Google Scholar 

  • Burrage LC, Tang S, Wang J, Donti TR, Walkiewicz M, Luchak JM, Chen LC, Schmitt ES, Niu Z, Erana R, Hunter JV, Graham BH, Wong LJ, Scaglia F. Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G > A) in the mitochondrial encoded ATP6 gene. Mol Genet Metab. 2014;113:207–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byrne MT, Bergman AK, Ruiz AI, Silver BJ, Maciejewski JP, Tiu RV. Postsplenectomy thromboembolic disease in congenital sideroblastic anaemia. BMJ Case Rep. 2010;2010:bcr1220092514. doi:10.1136/bcr.12.2009.2514.

    Google Scholar 

  • Cancer I. A. O. R. F. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumours of haematopoietic and lymphoid tissue (IARC WHO Classification of Tumours). 4th ed. Lyon: ARC Press; 2008.

    Google Scholar 

  • Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T, Durie D, Campagna DR, Lau A, Sendamarai AK, Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Wynn RF, Laxer RM, Minniti CP, Moppett J, Bordon V, Geraghty M, Joyce PB, Markianos K, Rudner AD, Holcik M, Fleming MD. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014;124:2867–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotter PD, May A, Li L, Al-Sabah AI, Fitzsimons EJ, Cazzola M, Bishop DF. Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood. 1999;93:1757–69.

    CAS  PubMed  Google Scholar 

  • Cousins RJ. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev. 1985;65:238–309.

    CAS  PubMed  Google Scholar 

  • Damm F, Kosmider O, Gelsi-Boyer V, Renneville A, Carbuccia N, Hidalgo-Curtis C, Della Valle V, Couronne L, Scourzic L, Chesnais V, Guerci-Bresler A, Slama B, Beyne-Rauzy O, Schmidt-Tanguy A, Stamatoullas-Bastard A, Dreyfus F, Prebet T, De Botton S, Vey N, Morgan MA, Cross NC, Preudhomme C, Birnbaum D, Bernard OA, Fontenay M, Groupe Francophone Des, M. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood. 2012;119:3211–8.

    Article  CAS  PubMed  Google Scholar 

  • Donker AE, Raymakers RA, Vlasveld LT, Van Barneveld T, Terink R, Dors N, Brons PP, Knoers NV, Swinkels DW. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis. Blood. 2014;123:3873–86; quiz 4005.

    Article  CAS  PubMed  Google Scholar 

  • Fleming MD. Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation. Hematol Am Soc Hematol Educ Program. 2011;2011:525–31.

    Google Scholar 

  • Fujiwara T, Harigae H. Pathophysiology and genetic mutations in congenital sideroblastic anemia. Pediatr Int. 2013;55:675–9.

    Article  CAS  PubMed  Google Scholar 

  • Germing U, Strupp C, Kuendgen A, Isa S, Knipp S, Hildebrandt B, Giagounidis A, Aul C, Gattermann N, Haas R. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica. 2006;91:1596–604.

    PubMed  Google Scholar 

  • Harigae H, Furuyama K. Hereditary sideroblastic anemia: pathophysiology and gene mutations. Int J Hematol. 2010;92:425–31.

    Article  CAS  PubMed  Google Scholar 

  • Kushner JP, Lee GR, Wintrobe MM, Cartwright GE. Idiopathic refractory sideroblastic anemia: clinical and laboratory investigation of 17 patients and review of the literature. Medicine (Baltimore). 1971;50:139–59.

    Article  CAS  Google Scholar 

  • Lazarchick J. Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol. 2012;19:58–60.

    Article  CAS  PubMed  Google Scholar 

  • Lorber A, Gazit AZ, Khoury A, Schwartz Y, Mandel H. Cardiac manifestations in thiamine-responsive megaloblastic anemia syndrome. Pediatr Cardiol. 2003;24:476–81.

    Article  CAS  PubMed  Google Scholar 

  • Malcovati L, Cazzola M. Refractory anemia with ring sideroblasts. Best Pract Res Clin Haematol. 2013;26:377–85.

    Article  CAS  PubMed  Google Scholar 

  • Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, Passamonti F, Arcaini L, Maffioli M, Bernasconi P, Lazzarino M, Cazzola M. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23:7594–603.

    Article  PubMed  Google Scholar 

  • Mozzillo E, Melis D, Falco M, Fattorusso V, Taurisano R, Flanagan SE, Ellard S, Franzese A. Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings. Pediatr Diabetes. 2013;14:384–7.

    Article  CAS  PubMed  Google Scholar 

  • Nikpour M, Scharenberg C, Liu A, Conte S, Karimi M, Mortera-Blanco T, Giai V, Fernandez-Mercado M, Papaemmanuil E, Hogstrand K, Jansson M, Vedin I, Stephen Wainscoat J, Campbell P, Cazzola M, Boultwood J, Grandien A, Hellstrom-Lindberg E. The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts. Leukemia. 2013;27:889–96.

    Article  CAS  PubMed  Google Scholar 

  • Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, Pellagatti A, Wainscoat JS, Hellstrom-Lindberg E, Gambacorti-Passerini C, Godfrey AL, Rapado I, Cvejic A, Rance R, Mcgee C, Ellis P, Mudie LJ, Stephens PJ, McLaren S, Massie CE, Tarpey PS, Varela I, Nik-Zainal S, Davies HR, Shlien A, Jones D, Raine K, Hinton J, Butler AP, Teague JW, Baxter EJ, Score J, Galli A, Della Porta MG, Travaglino E, Groves M, Tauro S, Munshi NC, Anderson KC, El-Naggar A, Fischer A, Mustonen V, Warren AJ, Cross NC, Green AR, Futreal PA, Stratton MR, Campbell PJ, Chronic Myeloid Disorders Working Group Of The International Cancer Genome, C. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011;365:1384–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patnaik MM, Lasho TL, Hodnefield JM, Knudson RA, Ketterling RP, Garcia-Manero G, Steensma DP, Pardanani A, Hanson CA, Tefferi A. SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood. 2012;119:569–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillips JD, Kushner JP. The porphyrias. In: Orkin SH, Nathan DG, Ginsburgh D, Look AT, Fisher DE, Samuel E, Lux I, editors. Nathan and Oski’s hematology of infancy and childhood. 7th ed. Philadelphia: Elsevier; 2009.

    Google Scholar 

  • Rialon KL, Speicher PJ, Ceppa EP, Rendell VR, Vaslef SN, Beaven A, Tyler DS, Blazer 3rd DG. Outcomes following splenectomy in patients with myeloid neoplasms. J Surg Oncol. 2015;111:389–95.

    Article  PubMed  Google Scholar 

  • Ricketts CJ, Minton JA, Samuel J, Ariyawansa I, Wales JK, Lo IF, Barrett TG. Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. Acta Paediatr. 2006;95:99–104.

    Article  PubMed  Google Scholar 

  • Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giege R, Bahlo M, Christodoulou J. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers ZR, Alter BP. Bone marrow failure syndromes. In: De Alarcon PA, J. W E, Christensen RD, editors. Neonatal hematology: pathogenesis, diagnosis, and management of hematologic problems. 2nd ed. New York: Cambridge University Press; 2013.

    Google Scholar 

  • Shaw-Smith C, Flanagan SE, Patch AM, Grulich-Henn J, Habeb AM, Hussain K, Pomahacova R, Matyka K, Abdullah M, Hattersley AT, Ellard S. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes. 2012;13:314–21.

    Article  CAS  PubMed  Google Scholar 

  • Sheftel AD, Richardson DR, Prchal J, Ponka P. Mitochondrial iron metabolism and sideroblastic anemia. Acta Haematol. 2009;122:120–33.

    Article  CAS  PubMed  Google Scholar 

  • Tanno T, Miller JL. Iron loading and overloading due to ineffective erythropoiesis. Adv Hematol. 2010;2010:358283.

    Article  PubMed  PubMed Central  Google Scholar 

  • Visconte V, Makishima H, Jankowska A, Szpurka H, Traina F, Jerez A, O’Keefe C, Rogers HJ, Sekeres MA, Maciejewski JP, Tiu RV. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia. 2012;26:542–5.

    Article  CAS  PubMed  Google Scholar 

  • Willekens C, Dumezy F, Boyer T, Renneville A, Rossignol J, Berthon C, Cotteau-Leroy A, Mehiaoui L, Quesnel B, Preudhomme C. Linezolid induces ring sideroblasts. Haematologica. 2013;98:e138–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Chakraborty P, Geraghty MT, Major-Cook N, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Fleming MD, Wynn RF. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013;122:112–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Children’s Specialty Group, 811 Redgate Ave., Norfolk, VA, 23507, USA

    Eric J. Werner MD, MMM

  2. Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA, USA

    Eric J. Werner MD, MMM

  3. Division of Pediatric Hematology/Oncology, Nationwide Children’s Hospital, Columbus, OH, USA

    Anthony D. Villella MD

  4. Department of Pediatrics, Ohio State School of Medicine, Columbus, OH, USA

    Anthony D. Villella MD

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  1. Eric J. Werner MD, MMM
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  2. Anthony D. Villella MD
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Correspondence to Anthony D. Villella MD .

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Editors and Affiliations

  1. Cancer Treatment Centers of America, Department of Hematology and Bone Marrow Transplantion, Zion, Illinois, USA

    Syed A. Abutalib

  2. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Jean M. Connors

  3. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    Margaret V. Ragni

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Werner, E.J., Villella, A.D. (2016). Sideroblastic Anemias: Diagnosis and Management. In: Abutalib, S., Connors, J., Ragni, M. (eds) Nonmalignant Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-30352-9_13

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