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

Diamond-Blackfan syndrome is a congenital hypoplastic anaemia that usually presents in infancy:¹

• Approximately 30% of patients have other congenital anomalies, particularly of the upper limb, craniofacial regions, heart, and urogenital tract.²
• Although the majority of cases are sporadic, approximately 10-25% are familial, with most showing autosomal dominant inheritance.³
• Leukocyte and platelet counts are normal or slightly reduced.
• The exact cause is not clear, but the problem seems to be a fault in one of the early steps of red blood cell production.

Epidemiology

• Diamond-Blackfan syndrome occurs in 5-10 babies per million births and in the UK it will affect an average of 7 babies born each year.
• It is inherited in about 10-20% of cases.⁴
• In about 15% of affected children there is a fault within a gene called 'ribosomal protein S19' (RPS19).⁵ There is evidence for involvement of at least two other genes.³
• In most cases, occurrence is sporadic but then, in subsequent generations, inheritance is usually autosomal dominant.

Presentation

• 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.
• 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.

Differential diagnosis

• Parvovirus infection.
• Transient erythroblastopenia of childhood.

Investigations

• Prenatal diagnosis is currently only possible if there is a mutation affecting RPS19.
• 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.

Management

• About 30% of children with Diamond-Blackfan syndrome will respond to oral prednisolone. However, this means that the child will have to take long-term steroid medication with inevitable long-term side effects and steroids may suddenly stop working at any time.
• Ciclosporin A in combination with prednisolone improves success rates and can be steroid-sparing.⁶
• 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.
• The only cure available for Diamond-Blackfan syndrome is bone marrow transplantation but this is not always successful and is usually reserved for patients who do not respond to steroids or blood transfusions.⁷
• A recent study in Japan found an 85% success rate with haematopoietic stem cell transplantation.⁸

Complications

There is an increased risk of leukaemia.⁹

Prognosis

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

Document references

1. Ellis SR, Lipton JM; Diamond Blackfan anemia: a disorder of red blood cell development. Curr Top Dev Biol. 2008;82:217-41. [abstract]
2. Campagnoli MF, Ramenghi U, Armiraglio M, et al; RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat. 2008 Jul;29(7):911-20. [abstract]
3. Diamond-Blackfan Anemia, Online Mendelian Inheritance in Man (OMIM)
4. Gazda HT, Sieff CA; Recent insights into the pathogenesis of Diamond-Blackfan anaemia.; Br J Haematol. 2006 Aug 31;. [abstract]
5. Orfali KA, Ohene-Abuakwa Y, Ball SE; Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity.; Br J Haematol. 2004 Apr;125(2):243-52. [abstract]
6. 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 Oct;110(4):e44. [abstract]
7. Roy V, Perez WS, Eapen M, et al; Bone marrow transplantation for diamond-blackfan anemia.; Biol Blood Marrow Transplant. 2005 Aug;11(8):600-8. [abstract]
8. Ohga S, Mugishima H, Ohara A, et al; Diamond-Blackfan anemia in Japan: clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation.; Int J Hematol. 2004 Jan;79(1):22-30. [abstract]
9. Alter BP, Giri N, Savage SA, et al; Malignancies and survival patterns in the National Cancer Institute inherited Br J Haematol. 2010 Jul;150(2):179-88. Epub 2010 Apr 30. [abstract]

Acknowledgements