Makindo Medical Notes

There is very strong evidence that Diamond-Blackfan Anemia (DBA) is inherited as an autosomal dominant disorder with variable penetrance and expressivity.

About

• Red cell failure usually presents in a child younger than 1 year.
• Presence of congenital anomalies. Cancer predisposition.

Epidemiology

• DBA is a rare disorder, with an estimated incidence of 5-7 per million live births.
• It predominantly affects males, though females can also be diagnosed.

Aetiology

• Results from haploinsufficiency of either a small or large subunit-associated ribosomal protein.
• Mutations in ribosomal protein genes (e.g., RPS19, RPL5, RPL11) are commonly implicated.

Clinical Features

• Anaemia within the first year of life.
• Short stature is found in many patients.
• Clinically significant anaemia at birth, and hydrops fetalis is rarely seen.
• Presence of congenital anomalies such as craniofacial, upper limb, and heart defects.
• Increased risk of malignancies, particularly acute myeloid leukemia and osteogenic sarcoma.

Differential Diagnoses

• Fanconi Anemia
• Transient Erythroblastopenia of Childhood
• Myelodysplastic Syndromes
• Other forms of Pure Red Cell Aplasia
• Iron Deficiency Anemia

Investigations

• Full Blood Count (FBC):
  • Macrocytic, or occasionally normocytic, anaemia with reticulocytopenia.
  • Essentially normal neutrophil and platelet counts.
• Fetal Haemoglobin (HbF) Level: May be elevated.
• Erythrocyte Adenosine Deaminase (eADA) Activity: Often elevated.
• Bone Marrow Examination:
  • Normocellular bone marrow with a paucity of erythroid precursors.
  • Helps exclude malignancy.
• Genetic Testing: For the DBA-associated genes (e.g., RPS19, RPL5).
• Immunological Tests: To rule out immune-mediated causes of Pure Red Cell Aplasia.

Management

• Patient management is therefore centred on accurate diagnosis.
• Appropriate use of transfusions and iron chelation to maintain Hb levels between 8 and 11 g/dL.
• Corticosteroids are given post-transfusion to stimulate erythropoiesis.
• Haematopoietic stem cell transplantation (HSCT) is considered in severe cases or those refractory to medical therapy.
• Regular monitoring for iron overload and potential complications.
• Management of congenital anomalies and cancer predisposition.

Prognosis

• With appropriate treatment, many patients achieve remission and normal RBC production.
• Chronic management may be necessary to maintain adequate haemoglobin levels.
• Increased risk of malignancies requires vigilant monitoring.
• Overall prognosis varies based on severity, response to treatment, and presence of congenital anomalies.

Conclusion

Diamond-Blackfan Anemia is a rare inherited disorder characterized by red cell aplasia and associated with various congenital anomalies and an increased risk of malignancies. Early diagnosis and comprehensive management, including transfusions, corticosteroids, and potentially haematopoietic stem cell transplantation, are essential for improving patient outcomes. Ongoing monitoring and supportive care are crucial to manage complications and enhance the quality of life for affected individuals.

References

• Blood Journal. Diamond-Blackfan Anemia: Clinical Features and Management. Available at: https://www.bloodjournal.org/content/116/19/3715?sso-checked=true#sec-2
• Mayo Clinic. Diamond-Blackfan Anemia. Available at: https://www.mayoclinic.org
• National Heart, Lung, and Blood Institute (NHLBI). Diamond-Blackfan Anemia. Available at: https://www.nhlbi.nih.gov
• World Health Organization (WHO). Diamond-Blackfan Anemia. Available at: https://www.who.int
• Arber, D. A., et al. (2019). Diagnosis and Classification of Myeloid Neoplasms and Acute Leukemia. Blood Journal.
• Kim, Y. B., et al. (2020). Diamond-Blackfan Anemia: An Update. Hematology/Oncology Clinics of North America.
• American Society of Hematology. Diamond-Blackfan Anemia. Available at: https://www.hematology.org