Diamond-Blackfan Syndrome

Synonyms: Diamond-Blackfan anaemia (DBA), Chronic Congenital Erythrogenesis Imperfecta

Diamond-Blackfan anaemia is a congenital hypoplastic anaemia that usually presents in infancy¹:

• 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 to 25% are familial, with most showing autosomal dominant inheritance.³
• Leucocyte 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.

• Diamond-Blackfan anaemia occurs in 5-10 babies per million births and in the UK it will affect an average of 7 babies born each year.
• Is inherited in about 10-20% of cases.⁴
• In about 15% of affected children there is a fault within a gene called RPS19 ('small ribosomal protein 19').⁵ There is evidence for involvement of at least two other genes.⁴
• 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 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.

• Parvovirus infection
• Transient erythroblastopenia of childhood

• 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.
• Full blood count and film shows 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 30% of children with Diamond-Blackfan anaemia 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 anaemia 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.^7,8
• A recent study in Japan found an 85% success rate with haematopoietic stem cell transplantation.⁹

There is an increased risk of leukaemia.¹⁰

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