Diamond-Blackfan Syndrome

Authored by , Reviewed by Dr Helen Huins | Last edited | Meets Patient’s editorial guidelines

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Synonyms: Diamond-Blackfan anaemia (DBA), chronic congenital erythrogenesis imperfecta

Diamond-Blackfan syndrome is a congenital hypoplastic anaemia that usually presents in infancy.[1, 2]

  • Approximately 30% of patients have other congenital anomalies, particularly of the upper limb, craniofacial regions, heart and urogenital tract.[3]
  • Although the majority of cases are sporadic, approximately 10-25% are familial, with most showing autosomal dominant inheritance.[4]
  • Leukocyte and platelet counts are normal or slightly reduced.[5]
  • The exact cause is not clear but there is a disorder of ribosome biogenesis.[6]
  • Diamond-Blackfan syndrome is one of a rare group of genetic disorders, known as the inherited bone marrow failure syndromes.[7]
  • In about 25% of affected children there is a fault within a gene called 'ribosomal protein S19' (RPS19).[8] There is evidence for involvement of a number of other genes.
  • In most cases, occurrence is sporadic but then, in subsequent generations, inheritance is usually autosomal dominant.
  • The severity of symptoms is variable but is often severe and life-threatening.
  • Usually it presents in the first few months of life when a young child develops a severely hypoplastic macrocytic anaemia.
  • Some children may not develop anaemia until later on in childhood.
  • Physical anomalies are present in up to 50% of affected infants. There is a wide range of severity.[9]
  • Hand deformities include a triphalangeal thumb and thenar muscle hypoplasia.
  • Many affected children are very short for their age and may have delayed puberty.
  • Development is otherwise normal and it is unusual for affected children to have learning difficulties.
  • Prenatal testing and carrier testing is possible if the mutation is known.[10]
  • The diagnosis is easy if there is already an affected child within the family, or the baby has a physical feature.
  • FBC and film show a normochromic anaemia but normal white cells and platelets. The red cell MCV is often high.
  • Bone marrow confirms aplasia and can be used to check for evidence of parvovirus infection, which should be excluded.
  • The enzyme adenosine deaminase (eADA) in the red blood cells is usually raised.
  • Radiological manifestations are those of the thumb malformation which is usually triphalangeal, and may be bifurcated, hypoplastic or subluxed.
  • About 80% of children with Diamond-Blackfan syndrome will initially respond to oral prednisolone. However, this means that the child will have to take long-term steroid medication with inevitable long-term side-effects.[11]
  • Ciclosporin A in combination with prednisolone improves success rates and can be steroid-sparing.[12]
  • If a person doesn't respond to steroid medication then blood transfusions are required. Survival of transfused erythrocytes is normal. Regular blood transfusions lead to problems of iron overload (and therefore iron chelating treatment with desferrioxamine is required).[11]
  • The only cure available for the haematological manifestations of Diamond-Blackfan syndrome is bone marrow transplantation.[10]This is not always successful and is usually reserved for patients who do not respond to steroids or blood transfusions.[13]

Side-effects from long-term steroids and iron overload associated with repeated blood transfusions.[11]

There is an increased risk of malignancies, including solid tumours and leukaemias.[6, 14]

  • Anaemia is often progressive and severe.
  • Spontaneous remission can occur but is rare.

Further reading and references

  1. Ellis SR; Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim Biophys Acta. 2014 Jun1842(6):765-8. doi: 10.1016/j.bbadis.2013.12.013. Epub 2014 Jan 8.

  2. Ellis SR, Lipton JM; Diamond Blackfan anemia: a disorder of red blood cell development. Curr Top Dev Biol. 200882:217-41.

  3. Campagnoli MF, Ramenghi U, Armiraglio M, et al; RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat. 2008 Jul29(7):911-20.

  4. Diamond-Blackfan Anemia 1, DBA1; Online Mendelian Inheritance in Man (OMIM)

  5. Gazda HT, Sieff CA; Recent insights into the pathogenesis of Diamond-Blackfan anaemia. Br J Haematol. 2006 Aug 31.

  6. Vlachos A, Rosenberg PS, Atsidaftos E, et al; Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood. 2012 Apr 19119(16):3815-9. doi: 10.1182/blood-2011-08-375972. Epub 2012 Feb 23.

  7. Lipton JM, Ellis SR; Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am. 2009 Apr23(2):261-82. doi: 10.1016/j.hoc.2009.01.004.

  8. Orfali KA, Ohene-Abuakwa Y, Ball SE; Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity. Br J Haematol. 2004 Apr125(2):243-52.

  9. Ball S; Diamond Blackfan anemia. Hematology Am Soc Hematol Educ Program. 20112011:487-91. doi: 10.1182/asheducation-2011.1.487.

  10. Clinton C, Gazda HT; Diamond-Blackfan Anemia. SourceGeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle 1993-2015. 2009 Jun 25 [updated 2014 Sep 4].

  11. Narla A, Vlachos A, Nathan DG; Diamond Blackfan anemia treatment: past, present, and future. Semin Hematol. 2011 Apr48(2):117-23. doi: 10.1053/j.seminhematol.2011.01.004.

  12. El-Beshlawy A, Ibrahim IY, Rizk S, et al; Study of 22 Egyptian patients with Diamond-Blackfan anemia, corticosteroids, and cyclosporin therapy results. Pediatrics. 2002 Oct110(4):e44.

  13. Roy V, Perez WS, Eapen M, et al; Bone marrow transplantation for diamond-blackfan anemia. Biol Blood Marrow Transplant. 2005 Aug11(8):600-8.

  14. Alter BP, Giri N, Savage SA, et al; Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol. 2010 Jul150(2):179-88. Epub 2010 Apr 30.