What is Diamond-Blackfan anemia?
Diamond-Blackfan anemia is a rare blood disorder in which the bone marrow, the spongy tissue in the center of the bones, does not produce an adequate amount of red blood cells, the cells that carry oxygen to the body. A diagnosis is usually made before the patient’s first birthday, but often times is not made until later in childhood. The disease gets its name from the two doctors who discovered it in the 1930s (Dr. Louis K. Diamond and Dr. Kenneth D. Blackfan).
Who is likely to be affected by Diamond-Blackfan anemia?
There is no group that is more or less prone to Diamond-Blackfan anemia, with the exception of those with a family history.
Symptoms and Causes
What causes Diamond-Blackfan anemia?
The disorder is inherited in up to one fourth of the cases. In most cases, the cause is not known. If a parent has Diamond-Blackfan anemia, his or her children have a 50% chance of also having the disorder.
What signs may lead a doctor to suspect Diamond-Blackfan anemia?
The signs are typical of those in patients with anemia – you may feel fatigued, have difficulty breathing, experience dizziness, or have a pale skin tone. A finding that is specific to Diamond-Blackfan anemia is the presence of abnormal features, most often the thumbs. About 25% of patients with Diamond-Blackfan anemia will have abnormal features. Children who are affected tend to be short for their age and may not reach puberty until relatively late.
Diagnosis and Tests
How is Diamond-Blackfan anemia diagnosed?
If Diamond-Blackfan anemia is suspected based on your symptoms and a physical examination, a complete blood count (CBC) may be done. The CBC includes measures of:
- Hemoglobin, the oxygen-carrying protein in red blood cells
- Hematocrit, which is the volume of red blood cells in blood
- Quantity (and size) of red blood cells
- Quantity of white blood cells
- Quantity of platelets
Low levels of any of these blood components may signal anemia.
A reticulocyte count, a measure of young red blood cells, may indicate that your bone marrow is not producing an adequate number of red blood cells.
A bone marrow aspiration and biopsy (removing a small amount of the liquid portion of bone marrow through a needle) along with genetic testing can confirm the diagnosis. If upon examination under a microscope the number of red cells in these samples is abnormally low, a diagnosis may be established.
Management and Treatment
What are the treatment options for Diamond-Blackfan anemia?
Corticosteroid treatment in the form of oral prednisone is usually the first treatment option. A corticosteroid will help the bone marrow make more red blood cells, with the goal of maintaining hemoglobin in the body at about 10 g/dL. Adjustments in the dose of the corticosteroid may be made during the first few weeks of treatment, depending on measures of red blood cells. A CBC and reticulocyte count made be done periodically during dose adjustments.
Side effects of corticosteroid use are more likely if high doses or prolonged courses are needed. Some side effects are more serious than others. Common side effects of systemic steroids include:
- Increased appetite, weight gain
- Sudden mood swings
- Muscle weakness
- Blurred vision
- Increased growth of body hair
- Easy bruising
- Lower resistance to infection
- Swollen, "puffy" face
- Osteoporosis (bone weakening disease)
- Worsening of diabetes
- High blood pressure
- Stomach irritation
- Nervousness, restlessness
- Having difficulty sleeping
- Cataracts or glaucoma
- Water retention, swelling
If the anemia is very severe and does not respond to steroid treatment, or if intolerable side effects to treatments occur, blood transfusions may be tried. Typically, they are scheduled every 4 to 6 weeks, but are sometimes required more frequently.
Blood transfusions may cause allergic side effects or a problem known as a delayed transfusion reaction in which donated blood cells rapidly break down. Over time, with multiple transfusions, red blood cell antibodies (if the red blood cells received do not perfectly match the recipient’s own cells) may develop. Extremely rarely, infections may occur.
Iron overload (excess iron from blood transfusions may be stored in organs, eventually causing damage to them) is a long-term complication of multiple blood transfusions.
Iron overload can be screened for by measuring serum ferritin (a blood test). The presence of iron in the heart and liver can be detected through the use of magnetic resonance imaging scans (MRI). Iron overload in the liver and heart may compromise the function of these organs and lead to other complications.
Chelation therapy is the removal of iron from the body in the case of iron overload from chronic blood transfusions. This is typically done with oral medications. However, sometimes intravenous infusions are needed.
Bone marrow (stem cell) transplant
Bone marrow transplant from a compatible donor can help restore the bone marrow’s ability to make red blood cells, and may be tried if corticosteroid treatment is not successful or causes unacceptable side effects. Bone marrow transplant is the only treatment that is curative for Diamond-Blackfan anemia.
Compatible means that the donor has the same types of proteins, called human leukocyte antigens (HLA), on the surface of their cells as the person with Diamond-Blackfan anemia who will be receiving the transplant. Potential donors, however, must be screened for the genes associated with Diamond-Blackfan anemia because these genes will be passed to the transplant recipient.
Most patients with Diamond-Blackfan anemia, however, lack a suitably matched sibling donor. In such cases, alternative donors outside the family who are HLA matches can often be found through registries. Other options are family members or unrelated donors who are not exact HLA matches, but the success rate declines further when these types of donors are used.
A bone marrow transplant is done in the hospital. Within about 1 month, the transplanted bone marrow stem cells will start to make new, healthy blood cells. A bone marrow transplant is accompanied by a risk of a graft rejection or a complication called graft-versus-host disease. Graft-versus-host disease is a reaction by the body to the new transplanted cells. The reaction may manifest as an inflammation of the skin, diarrhea, or liver disease. It most often occurs during the first few months after the transplant but can occur at any time after transplant, and may persist for months or years.