diamond blackfan anemia


Summary: A rare congenital hypoplastic anemia that usually presents early in infancy. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. (Curr Opin Hematol 2000 Mar;7(2):85-94)

Top Publications

  1. Choesmel V, Bacqueville D, Rouquette J, Noaillac Depeyre J, Fribourg S, Crétien A, et al. Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood. 2007;109:1275-83 pubmed
    ..These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits. ..
  2. Huh W, Gill J, Sheth S, Buchanan G. Pneumocystis carinii pneumonia in patients with Diamond-Blackfan anemia receiving high-dose corticosteroids. J Pediatr Hematol Oncol. 2002;24:410-2 pubmed
    ..Infants with Diamond-Blackfan anemia receiving prolonged corticosteroid therapy should receive P. carinii pneumonia prophylaxis, such as trimethoprim/sulfamethoxazole, and prophylaxis should continue during corticosteroid tapering. ..
  3. Flygare J, Aspesi A, Bailey J, Miyake K, Caffrey J, Karlsson S, et al. Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood. 2007;109:980-6 pubmed
    ..This defect was observed to a lesser extent in CD34+ cells from patients with DBA who have mutations in RPS19. ..
  4. Lipton J, Ellis S. Diamond Blackfan anemia 2008-2009: broadening the scope of ribosome biogenesis disorders. Curr Opin Pediatr. 2010;22:12-9 pubmed publisher
    b>Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid failure, congenital anomalies and predisposition to cancer...
  5. Gazda H, Sieff C. Recent insights into the pathogenesis of Diamond-Blackfan anaemia. Br J Haematol. 2006;135:149-57 pubmed
  6. Boria I, Quarello P, Avondo F, Garelli E, Aspesi A, Carando A, et al. A new database for ribosomal protein genes which are mutated in Diamond-Blackfan Anemia. Hum Mutat. 2008;29:E263-70 pubmed publisher
    ..The database will be supplemented with other DBA genes as soon as they are reported and their mutations are identified and it should be of assistance to clinicians and investigators involved in DBA research and care. ..
  7. Ganapathi K, Shimamura A. Ribosomal dysfunction and inherited marrow failure. Br J Haematol. 2008;141:376-87 pubmed publisher
    ..Molecular studies of ribosome biogenesis and function in each of these syndromes are discussed. Models of how impairment of ribosomal pathways might affect haematopoiesis and tumorigenesis are explored. ..
  8. Vlachos A, Ball S, Dahl N, Alter B, Sheth S, Ramenghi U, et al. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br J Haematol. 2008;142:859-76 pubmed publisher
    ..The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference. ..
  9. Ohga S, Mugishima H, Ohara A, Kojima S, Fujisawa K, Yagi K, et al. Diamond-Blackfan anemia in Japan: clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation. Int J Hematol. 2004;79:22-30 pubmed
    ..Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA. ..

More Information


  1. Choesmel V, Fribourg S, Aguissa Touré A, Pinaud N, Legrand P, Gazda H, et al. Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum Mol Genet. 2008;17:1253-63 pubmed publisher
  2. Quigley J, GAZDA H, Yang Z, Ball S, Sieff C, Abkowitz J. Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in Diamond-Blackfan anemia. Blood Cells Mol Dis. 2005;35:189-92 pubmed
    ..In 4 families, the disease linked exclusively to 1q31. Here, we report that the FLVCR gene on 1q31, which encodes a cytoplasmic heme exporter associated with red cell aplasia in cats, is not involved in DBA in these families. ..
  3. Flygare J, Olsson K, Richter J, Karlsson S. Gene therapy of Diamond Blackfan anemia CD34(+) cells leads to improved erythroid development and engraftment following transplantation. Exp Hematol. 2008;36:1428-35 pubmed publisher
  4. Leblanc T, Da Costa L, Marie I, Demolis P, Tchernia G. Metoclopramide treatment in DBA patients: no complete response in a French prospective study. Blood. 2007;109:2266-7 pubmed
  5. Dobson R. "Saviour sibling" is born after embryo selection in the United States. BMJ. 2003;326:1416 pubmed
  6. Hamaguchi I, Ooka A, Brun A, Richter J, Dahl N, Karlsson S. Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia. Blood. 2002;100:2724-31 pubmed
    ..Therefore, these findings suggest that gene therapy for RPS19-deficient patients with DBA using viral vectors that express the RPS19 gene is feasible. ..
  7. Jabr F, Aoun E, Azar C, Taher A. Diamond-Blackfan anemia responding to valproic acid. Blood. 2004;104:3415 pubmed
  8. Lipton J, Atsidaftos E, Zyskind I, Vlachos A. Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan Anemia Registry. Pediatr Blood Cancer. 2006;46:558-64 pubmed
    b>Diamond Blackfan anemia (DBA) is a heterogeneous genetic disorder characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer...
  9. Ebert B, Lee M, Pretz J, Subramanian A, Mak R, Golub T, et al. An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray. Blood. 2005;105:4620-6 pubmed
    ..Deficiency of RPS19 therefore blocks proliferation of immature erythroid progenitor cells, and dexamethasone activates proliferation of the same cell population through mechanisms independent of RPS19. ..
  10. Flygare J, Kiefer T, Miyake K, Utsugisawa T, Hamaguchi I, Da Costa L, et al. Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia. Blood. 2005;105:4627-34 pubmed
    ..This study shows for the first time that RPS19 silencing decreases the proliferative capacity of hematopoietic progenitors and leads to a defect in erythroid development. ..
  11. Idol R, Robledo S, DU H, Crimmins D, Wilson D, Ladenson J, et al. Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Blood Cells Mol Dis. 2007;39:35-43 pubmed
    ..subunit ribosomal protein 19 (RPS19) is mutated in about 25% of cases of the bone marrow failure syndrome Diamond Blackfan Anemia (DBA), a childhood disease characterized by failure of red cell production...
  12. Chatr aryamontri A, Angelini M, Garelli E, Tchernia G, Ramenghi U, Dianzani I, et al. Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia. Hum Mutat. 2004;24:526-33 pubmed
    ..Our findings indicate that NMD and nonstop decay affect the expression of mutated RPS19 genes; this may help to clarify genotype-phenotype correlations in DBA. ..
  13. Gazda H, Zhong R, Long L, Niewiadomska E, Lipton J, Ploszynska A, et al. RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations. Br J Haematol. 2004;127:105-13 pubmed
    ..Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency. ..
  14. Scott E, Haider A, Hord J. Growth hormone therapy for short stature in Diamond Blackfan anemia. Pediatr Blood Cancer. 2004;43:542-4 pubmed
    We report a 13-year-old male with Diamond Blackfan anemia and short stature...
  15. Dunbar A, Moore S, Hinson R. Fetal Diamond-Blackfan anemia associated with hydrops fetalis. Am J Perinatol. 2003;20:391-4 pubmed
    ..We conclude that DBA should be considered as a possible etiology for fetal anemia even in the absence of a family history of anemia. ..
  16. Flygare J, Karlsson S. Diamond-Blackfan anemia: erythropoiesis lost in translation. Blood. 2007;109:3152-4 pubmed
    ..Recent studies and emerging findings suggest that a malfunctioning translational machinery may be a cause of anemia in patients with DBA. ..
  17. Koga Y, Ohga S, Nomura A, Takada H, Hara T. Reduced gene expression of clustered ribosomal proteins in Diamond-Blackfan anemia patients without RPS19 gene mutations. J Pediatr Hematol Oncol. 2006;28:355-61 pubmed
    ..The reduced RP gene expression, by itself, may suggest an underlying mechanism of the constitutional anemia. ..
  18. Ellis S, Lipton J. Diamond Blackfan anemia: a disorder of red blood cell development. Curr Top Dev Biol. 2008;82:217-41 pubmed publisher
    b>Diamond Blackfan anemia (DBA) is an inherited hypoplastic anemia that typically presents in the first year of life...
  19. Matsson H, Davey E, Draptchinskaia N, Hamaguchi I, Ooka A, Leveen P, et al. Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation. Mol Cell Biol. 2004;24:4032-7 pubmed
    ..Our findings indicate that zygotes which are Rps19(-/-) do not form blastocysts, whereas one normal Rps19 allele in C57BL/6J mice is sufficient to maintain normal ribosomal and possibly extraribosomal functions. ..
  20. Rey M, Duffy S, Brown J, Kennedy J, Dick J, Dror Y, et al. Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis. Haematologica. 2008;93:1617-26 pubmed publisher
    ..Taken together, our results suggest enhanced alternative splicing of FLVCR1 transcripts and subsequent FLVCR1 insufficiency as an additional contributing factor to the erythropoietic defect observed in Diamond-Blackfan anemia. ..
  21. Robledo S, Idol R, Crimmins D, Ladenson J, Mason P, Bessler M. The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA. 2008;14:1918-29 pubmed publisher
    ..b>Diamond Blackfan anemia (DBA) is an inherited red cell aplasia caused by mutations in one of several r-proteins...
  22. Chen S, Warszawski J, Bader Meunier B, Tchernia G, Da Costa L, Marie I, et al. Diamond-blackfan anemia and growth status: the French registry. J Pediatr. 2005;147:669-73 pubmed
    ..This result addresses the question of the respective part, in the pathogenesis of GR, of the disease severity, illustrated by treatment dependence on the one hand and of the deleterious effects of long-term treatments on the other hand. ..
  23. Leger Silvestre I, Caffrey J, Dawaliby R, Alvarez Arias D, Gas N, Bertolone S, et al. Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis. J Biol Chem. 2005;280:38177-85 pubmed
    Approximately 25% of cases of Diamond Blackfan anemia, a severe hypoplastic anemia, are linked to heterozygous mutations in the gene encoding ribosomal protein S19 that result in haploinsufficiency for this protein...
  24. Campagnoli M, Garelli E, Quarello P, Carando A, Varotto S, Nobili B, et al. Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature. Haematologica. 2004;89:480-9 pubmed
    ..Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials. ..
  25. Hamaguchi I, Flygare J, Nishiura H, Brun A, Ooka A, Kiefer T, et al. Proliferation deficiency of multipotent hematopoietic progenitors in ribosomal protein S19 (RPS19)-deficient diamond-Blackfan anemia improves following RPS19 gene transfer. Mol Ther. 2003;7:613-22 pubmed
    ..These findings suggest that gene therapy for RPS19-deficient DBA is feasible. ..
  26. Dyer C. Couple allowed to select an embryo to save sibling. BMJ. 2004;329:592 pubmed
  27. Ohene Abuakwa Y, Orfali K, Marius C, Ball S. Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect. Blood. 2005;105:838-46 pubmed
    The erythroid defect in Diamond Blackfan anemia (DBA) is known to be intrinsic to the stem cell, but its molecular pathophysiology remains obscure...
  28. Henter J, Karlen J. Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. Blood. 2007;109:5157-9 pubmed
    ..We suggest that deferiprone not be prescribed to DBA patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered. ..
  29. Ellis S, Massey A. Diamond Blackfan anemia: A paradigm for a ribosome-based disease. Med Hypotheses. 2006;66:643-8 pubmed
    b>Diamond Blackfan anemia is characterized by a severe hypoplastic anemia and a heterogeneous collection of other clinical features...
  30. Gazda H, Kho A, Sanoudou D, Zaucha J, Kohane I, Sieff C, et al. Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells. 2006;24:2034-44 pubmed
    ..Downregulation of c-myb expression, which causes complete failure of fetal liver erythropoiesis in knockout mice, suggests a link between RPS19 mutations and reduced erythropoiesis in DBA. ..
  31. Bobey N, Carcao M, Dror Y, Freedman M, Dahl N, Woodman R. Sustained cyclosporine-induced erythropoietic response in identical male twins with diamond-blackfan anemia. J Pediatr Hematol Oncol. 2003;25:914-8 pubmed
    ..Clinically, the response has been sustained, and both patients have continued cyclosporine therapy and have been transfusion-independent for more than 27 months. ..
  32. Faivre L, Meerpohl J, Da Costa L, Marie I, Nouvel C, Gnekow A, et al. High-risk pregnancies in Diamond-Blackfan anemia: a survey of 64 pregnancies from the French and German registries. Haematologica. 2006;91:530-3 pubmed
    ..Pregnancies in DBA-affected women are at high risk, especially for complications likely to be of vascular-placental origin. Careful monitoring with prevention of severe anemia and early introduction of aspirin is suggested. ..
  33. Gazda H, Grabowska A, Merida Long L, Latawiec E, Schneider H, Lipton J, et al. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006;79:1110-8 pubmed
    ..This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA. ..
  34. Yaris N, Erduran E, Cobanoglu U. Hodgkin lymphoma in a child with Diamond Blackfan anemia. J Pediatr Hematol Oncol. 2006;28:234-6 pubmed
    b>Diamond Blackfan anemia (DBA) is a rare disease characterized by aplasia or hypoplasia of erythroid lineage. Normochromic, usually macrocytic, but occasionally normocytic anemia and reticulocytopenia are characteristic findings of DBA...
  35. Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D. Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat. 2007;28:1178-82 pubmed
    ..The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis. ..
  36. Miyake K, Utsugisawa T, Flygare J, Kiefer T, Hamaguchi I, Richter J, et al. Ribosomal protein S19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model of Diamond-Blackfan anemia. Stem Cells. 2008;26:323-9 pubmed
    ..These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA. ..
  37. Campagnoli M, Ramenghi U, Armiraglio M, Quarello P, Garelli E, Carando A, et al. RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat. 2008;29:911-20 pubmed publisher
    ..It is shown that patients with RPS19 mutations display a poorer response to steroids and a worse long-term prognosis compared to other DBA patients. ..
  38. Doherty L, Sheen M, Vlachos A, Choesmel V, O Donohue M, Clinton C, et al. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010;86:222-8 pubmed publisher
  39. Abkowitz J, Schaison G, Boulad F, Brown D, Buchanan G, Johnson C, et al. Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood. 2002;100:2687-91 pubmed
    ..Three individuals responded, suggesting that this therapeutic approach may benefit others. As with the index case, the anemia did not improve until 12 to 15 weeks of therapy had been completed. ..
  40. Kuliev A, Rechitsky S, Tur Kaspa I, Verlinsky Y. Preimplantation genetics: Improving access to stem cell therapy. Ann N Y Acad Sci. 2005;1054:223-7 pubmed
    ..Successful therapy with HLA-matched stem cells, obtained from these PGD children, has been achieved already for Diamond-Blackfan anemia hypohidrotic ectodermal dysplasia with immune deficiency and thalassemia. ..
  41. Parekh S, Perez A, Yang X, Billett H. Chronic parvovirus infection and G6PD deficiency masquerading as Diamond-Blackfan anemia. Am J Hematol. 2005;79:54-7 pubmed
  42. Verlinsky Y, Rechitsky S, Sharapova T, Morris R, Taranissi M, Kuliev A. Preimplantation HLA testing. JAMA. 2004;291:2079-85 pubmed
  43. Ebert B, Pretz J, Bosco J, Chang C, Tamayo P, Galili N, et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature. 2008;451:335-9 pubmed publisher
    ..These results indicate that the 5q- syndrome is caused by a defect in ribosomal protein function and suggest that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes. ..
  44. Pospisilova D, Cmejlova J, Hak J, Adam T, Cmejla R. Successful treatment of a Diamond-Blackfan anemia patient with amino acid leucine. Haematologica. 2007;92:e66-7 pubmed
  45. Akiyama M, Yanagisawa T, Yuza Y, Yokoi K, Ariga M, Fujisawa K, et al. Successful treatment of Diamond-Blackfan anemia with metoclopramide. Am J Hematol. 2005;78:295-8 pubmed
    ..Metoclopramide therapy should be considered in patients with refractory DBA before treatment-related complications develop...
  46. Gazda H, Sheen M, Vlachos A, Choesmel V, O Donohue M, Schneider H, et al. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008;83:769-80 pubmed publisher
  47. Angelini M, Cannata S, Mercaldo V, Gibello L, Santoro C, Dianzani I, et al. Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome. Hum Mol Genet. 2007;16:1720-7 pubmed
    ..Moreover, none of the mutated RPS19 analyzed in this study, including those proteins that appear localized into the nucleolus, is able to be assembled into mature ribosome. ..
  48. Farrar J, Nater M, Caywood E, McDevitt M, Kowalski J, Takemoto C, et al. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008;112:1582-92 pubmed publisher
    ..The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition. ..
  49. Proust A, Da Costa L, Rince P, Landois A, Tamary H, Zaizov R, et al. Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene. Hematol J. 2003;4:132-6 pubmed
    ..For the 10 novel mutations found in the rps19 gene, there were no obvious genotype-phenotype correlations. The transmission of the polymorphisms was en bloc and the studies did not suggest any clinical correlates at this stage. ..
  50. Da Costa L, Tchernia G, Gascard P, Lo A, Meerpohl J, Niemeyer C, et al. Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology. Blood. 2003;101:5039-45 pubmed
    ..The present findings enable us to document the nucleolar localization signals in RPS19 and help define the phenotypic consequences of some mutations in RPS19 in DBA. ..
  51. Cmejlova J, Dolezalova L, Pospisilova D, Petrtylova K, Petrak J, Cmejla R. Translational efficiency in patients with Diamond-Blackfan anemia. Haematologica. 2006;91:1456-64 pubmed
    ..Our results indicate that inefficient translation may be the main cause of DBA, and administration of leucine may be beneficial for at least some DBA patients. ..
  52. Sornjai W, Lithanatudom P, Erales J, Joly P, Francina A, Hacot S, et al. Hypermethylation of 28S ribosomal RNA in ?-thalassemia trait carriers. Int J Biol Macromol. 2017;94:728-734 pubmed publisher
    ..Hemoglobin E trait carriers also showed evidence of dysregulation. These results provide the first evidence that ribosome biogenesis is dysregulated in ?-thalassemia trait carriers. ..
  53. Ferretti M, Ghalei H, Ward E, Potts E, Karbstein K. Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements. Nat Struct Mol Biol. 2017;24:700-707 pubmed publisher
    ..Moreover, the simultaneous gain-of-function and loss-of-function phenotypes from Rps26-deficient ribosomes can explain the pathogenesis of DBA. ..