Understanding Sideroblastic Anemia: An Overview of Genetics, Epidemiology, Pathophysiology and Current Therapeutic Options

References

• Cartwright GE, Deiss A. Sideroblasts, siderocytes, and sideroblastic anemia. N Engl J Med. 1975;292(4):185–193. doi:10.1056/NEJM1975012329204051088923
   PubMed Web of Science ®Google Scholar
• Aivado M, Gattermann N, Rong A, et al. X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells Mol Dis. 2006;37:40–45. doi:10.1016/j.bcmd.2006.04.00316735131
   PubMed Web of Science ®Google Scholar
• Congress 97th. Public Law 97–414 - Jan.4, 1983; 1983 Available from: https://www.fda.gov/media/99546/download. Accessed 52, 2020.
   Google Scholar
• Anemias, Sideroblastic. National Organization for Rare Disorders (NORD); 2007 Available from: https://rarediseases.org/rare-diseases/anemias-sideroblastic/. Accessed 52, 2020.
   Google Scholar
• Sideroblastic anemia Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Available from: https://rarediseases.info.nih.gov/diseases/667/sideroblastic-anemia. Accessed 52, 2020.
   Google Scholar
• Cooley. T. A severe type of hereditary anemia with elliptocytosis. Interesting sequence of splenectomy. Am J Med Sci. 1945;209:561–568. doi:10.1097/00000441-194505000-00001
   Web of Science ®Google Scholar
• Orphanet: X linked sideroblastic anemia. Available from: https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=11087&Disease_Disease_Search_diseaseGroup=x-linked-sideroblastic-anemia&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group of diseases=X-linked-sideroblastic-anemia&title=X-linked sideroblastic anemia&search=Disease_Search_Simple. Accessed 52, 2020.
   Google Scholar
• Fleming MD. Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation. Hematol Am Soc Hematol Educ Program. 2011;2011(1):525–531. doi:10.1182/asheducation-2011.1.525
   Web of Science ®Google Scholar
• Bergmann AK, Campagna DR, McLoughlin EM, et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer. 2010;54(2):273–278. doi:10.1002/pbc.2224419731322
   PubMed Web of Science ®Google Scholar
• Ducamp S, Kannengiesser C, Touati M, et al. Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations. Hum Mutat. 2011;32(6):590–597. doi:10.1002/humu.2145521309041
   PubMed Web of Science ®Google Scholar
• The Human Gene Mutation Database; HGMD® gene result. Available from: http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ALAS2. Accessed 426, 2020.
   Google Scholar
• Abu-Zeinah G, DeSancho MT, Al-Kawaaz M, Geyer J. Delayed diagnosis of congenital sideroblastic anemia. Semin Hematol. 2018;55(4):177–178. doi:10.1053/j.seminhematol.2017.09.00130502842
   PubMed Web of Science ®Google Scholar
• Campagna DR, de Bie CI, Schmitz-Abe K, et al. X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. Am J Hematol. 2014;89(3):315–319. doi:10.1002/ajh.2361624166784
   PubMed Web of Science ®Google Scholar
• Kaneko K, Furuyama K, Fujiwara T, et al. Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia. Haematologica. 2014;99(2):252–261. doi:10.3324/haematol.2013.08544923935018
   PubMed Web of Science ®Google Scholar
• Cazzola M, May A, Bergamaschi G, Cerani P, Rosti VBD. Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. Blood. 2000;96(13):4363–4365. doi:10.1182/blood.V96.13.436311110715
   PubMed Web of Science ®Google Scholar
• Aivado M, Gattermann N, Bottomley S, Cazzola M, Bergamaschi G. X chromosome inactivation ratios in female carriers of X-linked sideroblastic anemia [3] (multiple letters). Blood. 2001;97(12):4000–4002. doi:10.1182/blood.V97.12.400011405213
   PubMed Web of Science ®Google Scholar
• Sankaran VG, Ulirsch JC, Tchaikovskii V, et al. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation. J Clin Invest. 2015;125(4):1665–1669. doi:10.1172/JCI7861925705881
   PubMed Web of Science ®Google Scholar
• Sankaran VG, Ulirsch JC, Tchaikovskii V, et al. Erratum: X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation (Journal of Clinical Investigation (2015) 125:4 (1665–1669) DOI: 10.1172/JCI78619). J Clin Invest. 2020;130(1):552. doi:10.1172/JCI132538
   Web of Science ®Google Scholar
• Cotter PD, May A, Fitzsimons EJ, et al. Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest. 1995;96(4):2090–2096. doi:10.1172/JCI1182587560104
   PubMed Web of Science ®Google Scholar
• Pondarre C, Campagna DR, Antiochos B, Sikorski L, Mulhern H, Fleming MD. Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood. 2007;109(8):3567–3569. doi:10.1182/blood-2006-04-01576817192398
   PubMed Web of Science ®Google Scholar
• 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(5):743–749. doi:10.1093/hmg/8.5.74310196363
   PubMed Web of Science ®Google Scholar
• Bekri S, Kispal G, Lange H, 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(9):3256–3264. doi:10.1182/blood.v96.9.3256.h8003256_3256_326411050011
   PubMed Web of Science ®Google Scholar
• The Human Gene Mutation Database; HGMD® gene result. Available from: http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ABCB7. Accessed 426, 2020.
   Google Scholar
• Lichtenstein DA, Crispin AW, Sendamarai AK, et al. A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. Blood. 2016;128(15):913–917. doi:10.1182/blood-2016-05-719062
   Web of Science ®Google Scholar
• Bergmann AK, Sahai I, Falcone JF, et al. Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. J Pediatr. 2009;155(6):888. doi:10.1016/j.jpeds.2009.06.01719643445
   PubMed Web of Science ®Google Scholar
• Oishi K, Hofmann S, Diaz GA, et al. Targeted disruption of Slc19a2, the gene encoding the high-affinity thiamin transporter Thtr-1, causes diabetes mellitus, sensorineural deafness and megaloblastosis in mice. Hum Mol Genet. 2002;11(23):2951–2960. doi:10.1093/hmg/11.23.295112393806
   PubMed Web of Science ®Google Scholar
• Boros LG, Steinkamp MP, Fleming JC, Lee WNP, Cascante M, Neufeld EJ. Defective RNA ribose synthesis in fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA). Blood. 2003;102(10):3556–3561. doi:10.1182/blood-2003-05-153712893755
   PubMed Web of Science ®Google Scholar
• Abboud MR, Alexander D, Najjar SS. Diabetes mellitus, thiamine-dependentmegaloblastic anemia, and sensorineural deafness associated with deficient α-ketoglutarate dehydrogenase activity. J Pediatr. 1985;107(4):537–541. doi:10.1016/S0022-3476(85)80011-14045602
   PubMed Web of Science ®Google Scholar
• Guernsey DL, Jiang H, Campagna DR, et al. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet. 2009;41(6):651–653. doi:10.1038/ng.35919412178
   PubMed Web of Science ®Google Scholar
• Chakraborty PK, Schmitz-Abe K, Kennedy EK, et al. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014;124(18):2867–2871. doi:10.1182/blood-2014-08-59137025193871
   PubMed Web of Science ®Google Scholar
• Rademakers LHPM, Koningsberger JC, Sorber CWJ, La Faille HBD, Van Hattum J, Marx JJM. Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria. Eur J Clin Invest. 1993;23(2):130–138. doi:10.1111/j.1365-2362.1993.tb00752.x8462622
   PubMed Web of Science ®Google Scholar
• Ye H, Jeong SY, Ghosh MC, 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(5):1749–1761. doi:10.1172/JCI4037220364084
   PubMed Web of Science ®Google Scholar
• Crispin A, Schmidt P, Campagna D, et al. Hscb, a mitochondrial iron-sulfur cluster assembly co-chaperone, is a novel candidate gene for congenital sideroblastic anemia. Blood. 2017;130(Supplement 1):79. doi:10.1182/BLOOD.V130.SUPPL_1.79.79
   Google Scholar
• Schmitz-Abe K, Ciesielski SJ, Schmidt PJ, et al. Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9. Blood. 2015;126(25):2734–2738. doi:10.1182/blood-2015-09-65985426491070
   PubMed Web of Science ®Google Scholar
• Wingert RA, Galloway JL, Barut B, et al. Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature. 2005;436(7053):1035–1039. doi:10.1038/nature0388716110529
   PubMed Web of Science ®Google Scholar
• Burrage LC, Tang S, Wang J, et al. 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(3):207–212. doi:10.1016/j.ymgme.2014.06.00425037980
   PubMed Web of Science ®Google Scholar
• Pearson HA, Lobel JS, Kocoshis SA, et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr. 1979;95(6):976–984. doi:10.1016/S0022-3476(79)80286-3501502
   PubMed Web of Science ®Google Scholar
• Rötig A, Bourgeron T, Chretien D, Rustin P, Munnich A. Spectrum of mitochondrial DNA rearrangements in the pearson marrow-pancreas syndrome. Hum Mol Genet. 1995;4(8):1327–1330. doi:10.1093/hmg/4.8.13277581370
   PubMed Web of Science ®Google Scholar
• Malcovati L, Karimi M, Papaemmanuil E, et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015;126(2):233–241. doi:10.1182/blood-2015-03-63353725957392
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts. N Engl J Med. 2011;365(15):1384–1395. doi:10.1056/NEJMoa110328321995386
   PubMed Web of Science ®Google Scholar
• Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405. doi:10.1182/blood-2016-03-64354427069254
   PubMed Web of Science ®Google Scholar
• Savage D, Lindenbaum J. Anemia in alcoholics. Med (United States). 1986;65(5):322–338. doi:10.1097/00005792-198609000-00005
   Web of Science ®Google Scholar
• Hines JD, Cowan DH. Studies on the pathogenesis of alcohol-induced sideroblastic bone-marrow abnormalities. N Engl J Med. 1970;283(9):441–446. doi:10.1056/NEJM1970082728309015434110
   PubMed Web of Science ®Google Scholar
• Konopka L, Hoffbrand AV. Haem synthesis in sideroblastic anaemia. Br J Haematol. 1979;42(1):73–83. doi:10.1111/j.1365-2141.1979.tb03699.x465361
   PubMed Web of Science ®Google Scholar
• Willekens C, Dumezy F, Boyer T, et al. Linezolid induces ring sideroblasts. Haematologica. 2013;98(11):e138–e140. doi:10.3324/haematol.2013.09239524186315
   PubMed Web of Science ®Google Scholar
• Beck EA, Ziegler G, Schmid R, Lüdin H. Reversible sideroblastic anemia caused by chloramphenicol. Acta Haematol. 1967;38(1):1–10. doi:10.1159/0002089944963348
   PubMed Web of Science ®Google Scholar
• Hastka J, Lasserre JJ, Schwarzbeck AHR. Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem. 1994;40(5):768–773. doi:10.1093/clinchem/40.5.7688174250
   PubMed Web of Science ®Google Scholar
• Bottomley SS. Pathophysiology of heme synthesis. Semin Hematol. 1988;25(4):282.3064310
   PubMed Web of Science ®Google Scholar
• Moore MR, Goldberg A, Yeung-Laiwah AAC. Lead effects on the heme biosynthetic pathway relationship to toxicity. Ann N Y Acad Sci. 1987;514(1 Mechanisms of):191–203. doi:10.1111/j.1749-6632.1987.tb48774.x3442384
   PubMed Web of Science ®Google Scholar
• Cousins RJ. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev. 1985;65(2):238–309. doi:10.1152/physrev.1985.65.2.2383885271
   PubMed Web of Science ®Google Scholar
• Fiske DN, McCoy HE, Kitchens CS. Zinc-induced sideroblastic anemia: report of a case, review of the literature, and description of the hematologic syndrome. Am J Hematol. 1994;46(2):147–150. doi:10.1002/ajh.28304602178172183
   PubMed Web of Science ®Google Scholar
• Simon SR, Branda RF, Tindle BH, Burns SL. Copper deficiency and sideroblastic anemia associated with zinc ingestion. Am J Hematol. 1988;28(3):181–183. doi:10.1002/ajh.28302803103407636
   PubMed Web of Science ®Google Scholar
• Williams DM, Loukopoulos D, Lee GR, Cartwright GE. Role of copper in mitochondrial iron metabolism. Blood. 1976;48(1):77–85. doi:10.1182/blood.V48.1.77.77947406
   PubMed Web of Science ®Google Scholar
• Piso RJ, Kriz K, Desax MC. Severe isoniazid related sideroblastic anemia. Hematol Rev. 2011;3(1):3–4. doi:10.4081/hr.2011.e2
   Google Scholar
• Santini V, Almeida A, Giagounidis A, et al. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. J Clin Oncol. 2016;34(25):2988–2996. doi:10.1200/JCO.2015.66.011827354480
   PubMed Web of Science ®Google Scholar
• Raza A, Reeves JA, Feldman EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93. doi:10.1182/blood-2007-01-06883317893227
   PubMed Web of Science ®Google Scholar
• Patnaik MM, Tefferi A. Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis: “2019 Update on Diagnosis, Risk-stratification, and Management.”. Am J Hematol. 2019;94(4):475–488. doi:10.1002/ajh.2539730618061
   PubMed Web of Science ®Google Scholar
• Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–151. doi:10.1056/NEJMoa190889231914241
   PubMed Web of Science ®Google Scholar
• Bachmeyer C, Ferroir JP, Eymard B, Maïer-Redelsperger M, Lebre AS, Girot R. Coenzyme Q is effective on anemia in a patient with sideroblastic anemia and mitochondrial myopathy. Blood. 2010;116(18):3681–3682. doi:10.1182/blood-2010-07-29945321051567
   PubMed Web of Science ®Google Scholar
• Kasapkara ÇS, Tümer L, Zanetti N, Ezgü F, Lamantea E, Zeviani M. A myopathy, lactic acidosis, sideroblastic anemia (MLASA) case due to a novel PUS1 mutation. Turk J Hematol. 2017;34(4):376–377. doi:10.4274/tjh.2017.0231
   Web of Science ®Google Scholar
• Gagne KE, Ghazvinian R, Yuan D, et al. Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood. 2014;124(3):437–440. doi:10.1182/blood-2014-01-54583024735966
   PubMed Web of Science ®Google Scholar
• Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol. 2008;143(1):27–38. doi:10.1111/j.1365-2141.2008.07290.x18637800
   PubMed Web of Science ®Google Scholar
• Furuyama K, Kaneko K. Iron metabolism in erythroid cells and patients with congenital sideroblastic anemia. Int J Hematol. 2018;107(1):44–54. doi:10.1007/s12185-017-2368-029139060
   PubMed Web of Science ®Google Scholar
• Cotter PD, May A, Li L, et al. 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(5):1757–1769. doi:10.1182/blood.V93.5.175710029606
   PubMed Web of Science ®Google Scholar
• Bottomley SS. Congenital sideroblastic anemias. Curr Hematol Rep. 2006;5(1):41–49.16537045
   PubMedGoogle Scholar
• Camaschella C, Campanella A, De Falco L, et al. The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood. 2007;110(4):1353–1358. doi:10.1182/blood-2007-02-07252017485548
   PubMed Web of Science ®Google Scholar
• Di Tucci AA, Murru R, Alberti D, Rabault B, Deplano S, Angelucci E. Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade, ICL670). Eur J Haematol. 2007;78(6):540–542. doi:10.1111/j.1600-0609.2007.00840.x17391307
   PubMed Web of Science ®Google Scholar
• Angelucci E, Barosi G, Camaschella C, et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders. Haematologica. 2008;93(5):741–752. doi:10.3324/haematol.1241318413891
   PubMed Web of Science ®Google Scholar
• Bottomley SS, Fleming MD. Sideroblastic anemia diagnosis and management. Hematol Oncol Clin North Am. 2014;28(4):653–670. doi:10.1016/j.hoc.2014.04.00825064706
   PubMed Web of Science ®Google Scholar
• Kim MH, Shah S, Bottomley SS, Shah NC. Reduced-toxicity allogeneic hematopoietic stem cell transplantation in congenital sideroblastic anemia. Clin Case Rep. 2018;6(9):1841–1844. doi:10.1002/ccr3.166730214775
   PubMed Web of Science ®Google Scholar