Diamond-Blackfan syndrome

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

What is Diamond-Blackfan syndrome?

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.⁴

• The exact cause is not clear but there is a disorder of ribosome biogenesis.⁵

Diamond-Blackfan syndrome epidemiology³

• Diamond-Blackfan syndrome is one of a rare group of genetic disorders, known as the inherited bone marrow failure syndromes.⁶

• In about 70-80% of affected children there is a fault within the ribosomal protein (RP) genes.⁷ There is evidence for involvement in 20 RP genes.

• In most cases, occurrence is sporadic but then, in subsequent generations, inheritance is usually autosomal dominant.

Diamond-Blackfan syndrome symptoms (Presentation)⁴

• 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.⁸

• 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 testing and carrier testing is possible if the mutation is known.⁹

• 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.

Diamond-Blackfan syndrome treatment and management¹⁰

• 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

• 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.⁹ This is not always successful and is usually reserved for patients who do not respond to steroids or blood transfusions.

Complications

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.^{5 12}

Prognosis

• Anaemia is often progressive and severe.

• Spontaneous remission can occur but is rare.