Anemia, Diamond–Blackfan

Diamond–Blackfan Anemia

Diamond–Blackfan Anemia (DBA) is a rare genetic disorder characterized by failure of the bone marrow to produce red blood cells, leading to anemia. It is classified as a congenital hypoplastic anemia and is typically diagnosed in infancy or early childhood.

Overview

Diamond–Blackfan Anemia is named after the pediatricians Louis K. Diamond and Kenneth Blackfan, who first described the condition in 1938. The disorder is part of a group of diseases known as bone marrow failure syndromes.

Etiology

DBA is primarily caused by mutations in genes that encode ribosomal proteins. These mutations lead to defects in ribosome biogenesis, which in turn affects the production of red blood cells. The most commonly affected gene is RPS19, but mutations in other ribosomal protein genes such as RPL5, RPL11, and RPS24 have also been implicated.

Clinical Features

Patients with Diamond–Blackfan Anemia typically present with severe macrocytic anemia, which is characterized by larger than normal red blood cells. Other clinical features may include:

• Physical anomalies such as craniofacial dysmorphism, thumb abnormalities, and short stature.
• Increased risk of developing malignancies, particularly acute myeloid leukemia and osteosarcoma.
• Growth retardation and developmental delays in some cases.

Diagnosis

The diagnosis of DBA is based on clinical findings, laboratory tests, and genetic analysis. Key diagnostic criteria include:

• Severe macrocytic anemia with reticulocytopenia (low reticulocyte count).
• Normal or slightly reduced white blood cell and platelet counts.
• Bone marrow examination showing a paucity of erythroid precursors.
• Genetic testing to identify mutations in ribosomal protein genes.

Management

Management of Diamond–Blackfan Anemia involves supportive care and specific treatments, including:

• Corticosteroids: Often the first line of treatment to stimulate red blood cell production.
• Blood transfusions: Used to manage anemia in patients who do not respond to corticosteroids.
• Hematopoietic stem cell transplantation: Considered in severe cases or when other treatments fail.
• Iron chelation therapy: To manage iron overload resulting from repeated blood transfusions.

Prognosis

The prognosis for individuals with DBA varies. Some patients respond well to treatment and lead relatively normal lives, while others may experience significant complications. Lifelong monitoring is essential to manage anemia and associated risks.

Genetic Counseling

Genetic counseling is recommended for families affected by DBA, as the condition can be inherited in an autosomal dominant manner. Prenatal testing and preimplantation genetic diagnosis may be options for families with known mutations.

Research and Future Directions

Ongoing research aims to better understand the pathophysiology of DBA and develop targeted therapies. Advances in gene therapy and molecular medicine hold promise for future treatment options.

Also see

• Anemia
• Bone marrow failure syndrome
• Ribosomal protein
• Hematopoietic stem cell transplantation