Constitutional deficiency anemia

Constitutional deficiency anemia, also known as Blackfan-Diamond anemia or Diamond-Blackfan anemia (DBA), is a rare inherited bone marrow failure syndrome characterized by a selective deficiency of red blood cell precursors (pure red cell aplasia) that typically presents in infancy or early childhood. The condition primarily affects the hematopoietic (blood-forming) system, leading to severe macrocytic anemia, often detected within the first year of life. Approximately 30-50% of affected individuals also have congenital anomalies, which may include craniofacial malformations (such as a flat nasal bridge and micrognathia), upper limb abnormalities (particularly thumb anomalies), cardiac defects, and short stature. Growth retardation is common. The disease is caused by mutations in genes encoding ribosomal proteins, with RPS19 being the most commonly affected gene (approximately 25% of cases). Other implicated genes include RPL5, RPL11, RPL35A, RPS10, RPS17, RPS24, and RPS26, among others. These mutations lead to impaired ribosome biogenesis, which particularly affects erythroid progenitor cells. Inheritance is autosomal dominant in most familial cases, though approximately 40-45% of cases arise from de novo mutations. Treatment options include corticosteroid therapy (typically prednisone), which is effective in approximately 80% of patients initially, though some patients become steroid-refractory or steroid-dependent over time. Chronic red blood cell transfusions with iron chelation therapy are used for patients who do not respond to corticosteroids. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment and is considered particularly for transfusion-dependent patients with a suitable donor. Patients with DBA have an increased risk of developing myelodysplastic syndrome, acute myeloid leukemia, and certain solid tumors, necessitating long-term monitoring.

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