Diamond Blackfan Anemia

Diamond Blackfan anaemia (DBA) is a congenital pure red cell aplasia from ribosomal protein defects.

• Incidence 5 to 7 per million live births; presentation in the first year in over 90%.
• Mutations in ribosomal protein genes (RPS19 in 25%, RPL5, RPL11, RPS26, RPL35A, GATA1, TSR2); autosomal dominant or de novo.
• Congenital anomalies in 50%: craniofacial (cleft palate, hypertelorism), thumb abnormalities (triphalangeal thumb), cardiac, urogenital, short stature.
• Raised red cell adenosine deaminase and fetal haemoglobin.
• Cancer predisposition (MDS, AML, osteosarcoma, colon cancer).

• Pallor, poor feeding, tachypnoea in early infancy, hydrops fetalis rarely.
• Normal white count and platelets (mild neutropenia in some).
• Physical anomalies, short stature, growth impairment (exacerbated by steroids).
• Complications of transfusion: iron overload.

• Macrocytic anaemia, reticulocytopenia, normal white count and platelets, raised HbF and MCV.
• Bone marrow: erythroid hypoplasia with normal myeloid and megakaryocytic lines.
• Elevated erythrocyte adenosine deaminase activity (85% sensitivity).
• Genetic testing panel (RPS19 deletion/duplication analysis and next generation sequencing).
• Exclude TEC, Fanconi anaemia, parvovirus, Pearson syndrome, drug effect.

• Corticosteroids: prednisolone 2 mg/kg/day until haemoglobin above 9 to 10 g/dL (2 to 4 weeks), then taper by 10 to 25% every 2 weeks to the lowest effective dose (under 0.5 mg/kg/day, ideally alternate day). Start after 12 months of age to protect growth. About 80% respond; 40% remain steroid dependent.
• Transfusion dependence (or steroid failure): packed red cells every 3 to 5 weeks to keep haemoglobin above 8 to 9 g/dL; iron chelation (deferasirox 20 to 30 mg/kg daily or deferoxamine 40 mg/kg SC) when ferritin above 1000 µg/L or after 10 to 20 transfusions.
• Leucine, sirolimus and other agents are experimental.
• Haematopoietic stem cell transplant from matched sibling donor for transfusion dependent patients under 10 years (survival over 90%); genotype sibling donors to exclude carriers.
• Monitor growth, bone density, glucose, blood pressure; annual surveillance for MDS/AML and solid tumours from adolescence.
• Genetic counselling, screening of relatives.