Diamond-Blackfan anemia (DBA) is a rare, inherited disorder affecting the bone marrow. It primarily hinders the bone marrow’s ability to produce sufficient red blood cells, which carry oxygen throughout the body. A deficiency in these cells leads to anemia, characterized by symptoms such as fatigue and pale skin. DBA is typically diagnosed during infancy or early childhood, often within the first year of life.
Causes and Genetics of Diamond-Blackfan Anemia
Diamond-Blackfan anemia is a genetic disorder stemming from mutations in specific genes involved in ribosome production. Ribosomes are cellular components that create proteins. These genetic changes lead to a decrease in red blood cell production, resulting in anemia.
About 40% to 45% of DBA cases are inherited from a parent in an autosomal dominant pattern; 55% to 60% occur as new, spontaneous mutations. One of the most frequently implicated genes is RPS19, which accounts for mutations in about 25% of DBA cases. Mutations in more than 11 different ribosomal and non-ribosomal genes have been identified in over half of children with DBA.
Symptoms and Diagnosis
Children with Diamond-Blackfan anemia often exhibit symptoms very early in life, typically leading to a diagnosis before their first birthday. The symptoms can vary in severity and generally fall into two categories. Anemia-related symptoms include pale skin, persistent fatigue, generalized weakness, and a rapid heartbeat. Infants might also show poor appetite and tiredness during feeding.
Approximately 47% of individuals with DBA also present with physical abnormalities. These may include craniofacial differences, such as a small head, small or low-set ears, or a cleft palate. Limb abnormalities are also common, affecting the thumb or other upper limbs. Other possible physical findings include short stature, heart problems, and kidney issues.
The diagnostic process for DBA begins with a complete blood count (CBC). This blood test reveals low red blood cell counts and a reduced number of reticulocytes (immature red blood cells), while white blood cell and platelet counts usually remain normal. Following the blood work, a bone marrow examination (biopsy and aspirate) is performed. This procedure confirms the failure of red blood cell precursor production within the bone marrow. Finally, genetic testing confirms the diagnosis by identifying a causative gene mutation.
Medical Management and Therapies
Medical management for Diamond-Blackfan anemia focuses on addressing the lack of red blood cells through several therapeutic approaches. Corticosteroids are a primary treatment to stimulate the bone marrow to produce more red blood cells. While these medications can effectively raise red blood cell counts in some patients, not all individuals respond to corticosteroid therapy.
For patients who do not respond to corticosteroids, regular blood transfusions become the primary therapy. This involves receiving infusions of red blood cells to manage anemia and alleviate its symptoms. Although transfusions are effective in improving oxygen delivery, they do not address the underlying cause of DBA and are not a cure.
Hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for Diamond-Blackfan anemia. This complex procedure involves replacing the patient’s faulty bone marrow with healthy bone marrow from a compatible donor. HSCT carries significant risks, including infection and graft-versus-host disease, and is reserved for patients who have not responded to other treatments or who have a severe form of the disease.
Associated Health Risks
Individuals with Diamond-Blackfan anemia face several long-term health risks, some related to treatments. A significant complication arising from chronic blood transfusions is iron overload, also known as hemosiderosis. The body cannot excrete excess iron from frequent transfusions, leading to its accumulation in organs like the heart, liver, and endocrine glands. To manage this, chelation therapy uses medications that bind to and remove excess iron from the body.
Beyond treatment-related issues, individuals with DBA have an increased risk of certain cancers. This elevated risk is associated with the underlying genetic defects of the disorder. Specific cancers seen more frequently in DBA patients include acute myeloid leukemia (AML) and various solid tumors, such as osteosarcoma. Regular monitoring for these potential complications is an ongoing aspect of care for DBA patients.