What is Diamond Blackfan anemia syndrome?

Diamond Blackfan anemia (DBA) syndrome is a rare blood disorder. Children with DBA syndrome don’t make enough red blood cells, which are the cells that carry oxygen to all other cells in the body.

Blood cells are made in the bone marrow, which is the spongy inside of long bones. In children with DBA syndrome, many of the cells that would have become red blood cells die before they develop.

What causes Diamond Blackfan anemia syndrome?

DBA syndrome is caused by a gene defect, usually in a ribosomal protein gene. Ribosomal proteins are found in every cell of the body, so when one protein is not produced in the full amount, DBA syndrome results.

• DBA syndrome may be passed down through families in about 40% of patients.
• In the other 60% of patients, the genetic cause is only present in the patient and not in the parents.
• Ribosomal protein gene defects are found in about 85% of people with DBA syndrome.
• In the other 15%, no gene defects are found and the cause isn’t defined yet, but research is being done to find the genetic cause in these patients.

What are the symptoms of Diamond Blackfan anemia syndrome?

Most of the time, symptoms of anemia (low hemoglobin) appear by the time a child is 2 months old. Symptoms may range from mild to severe. They include:

• Pale skin
• Sleepiness
• Being grouchy (irritability)
• Rapid heartbeat
• Heart murmur
• Physical defects of the face, head, neck, hands, kidneys and heart
• Low birth weight and/or poor weight gain

Some patients with DBA syndrome may not exhibit any symptoms of anemia, while others may also have low neutrophils (a type of white blood cell that helps fight bacterial infections), low platelets (components of the blood that form clots to stop bleeding), immunodeficiency and congenital abnormalities, such as abnormalities of the face, heart and/or kidneys.

Some patients may have poor growth and be shorter than others their age without DBA syndrome. Patients with DBA syndrome also have an increased risk of being diagnosed with cancer at an earlier age.

How is Diamond Blackfan anemia syndrome diagnosed?

The diagnosis of DBA syndrome is often made in the first year of life. It is diagnosed based on symptoms and on the results of blood and bone marrow testing.

Anemia is diagnosed with:

• Hemoglobin and hematocrit testing. This blood test measures the amount of hemoglobin (the protein in red blood cells that delivers oxygen to the tissues in the body) and red blood cells in the blood. (Hematocrit refers to the percentage by volume of red blood cells in a person’s body.)
• Complete blood count (CBC). This test checks red blood cells, white blood cells and platelets (blood clotting components). It sometimes checks young red blood cells (reticulocytes). It includes hemoglobin and hematocrit and more details about the red blood cells.
• Peripheral smear. A small sample of blood is checked under a microscope to see if the cells look normal.
• Bone marrow analysis. A sample of bone marrow cells is taken and examined to see if the production of red blood cells is normal.

Diagnosis of DBA syndrome is based on the following results from a CBC and bone marrow analysis:

• Anemia with low hemoglobin
• Red blood cells that are larger than normal (macrocytic)
• Low reticulocyte count (few new red blood cells)
• Bone marrow sample with only a few cells that will develop into red blood cells

The diagnosis of DBA syndrome is also made with genetic testing that is positive for a mutation in one of the DBA genes. A patient can be positive for the mutation and not be anemic. Other lab tests may also be abnormal.

An ultrasound of the kidneys and an echocardiogram of the heart should be done to look for congenital (birth) defects.

How is Diamond Blackfan anemia syndrome treated?

Treatment may include medicines, blood transfusions and bone marrow transplant. As more successful treatments have been developed, many children with DBA syndrome live well into adulthood, and many more adults now are living with the disease.

Specialists treat children with DBA syndrome. Your child’s health-care provider may advise seeing a blood specialist (hematologist), a gene specialist (geneticist) or other experts. DBA syndrome is treated with:

• Corticosteroid (also called steroid) medicines. Steroids improve anemia and red blood cell counts in about 80% of patients with DBA syndrome. Steroids are strong medicines with potentially serious side effects. Your child’s doctor will watch for side effects, and the patient should be maintained on as low a dose as possible. Steroid therapy may be lifelong for many patients with DBA syndrome.
• Blood transfusions. Blood transfusions are often needed for anemia at diagnosis and usually for the first year of life. Transfusions may be given every three to four weeks as needed to increase the red blood cell count and provide adequate hemoglobin for growth and development. For patients who do not ultimately respond to treatment with steroids, blood transfusions are life-long along with management of iron overload. These patients may be candidates for a stem cell transplant, or potentially gene therapy.
• Stem cell transplant. Stem cells are cells in the bone marrow that can become all types of blood cells. If an appropriate matched donor is found, then the donor’s stem cells are given to the person with DBA syndrome. This may be a close family member such as the patient’s brother or sister, but the donor must be confirmed to not have DBA syndrome first. Sometimes an unrelated stem cell donor is used. A successful stem cell transplant will alleviate the anemia of DBA syndrome. However, rejection or infection is possible. These and other risks can be serious, so stem cell transplant is usually only done if steroids are not effective and the patient is receiving red cell transfusions every 3-4 weeks.

About 20% of people with DBA syndrome become treatment independent. Treatment independence means that the symptoms of anemia have resolved without any treatment for more than six months. Treatment independence can last for many years. If symptoms come back, then the patient will require treatment with steroids or transfusions again.

What are possible complications of Diamond Blackfan anemia syndrome?

Complications of DBA syndrome may include:

• Slow or delayed growth
• Problems with pregnancy
• Problems related to physical defects (for instance, heart problems)
• Leukemia, colorectal cancer, bone cancer, breast cancer and other cancers

Some complications from DBA syndrome treatments include:

• Problems from long-term steroid use. If patients are on high doses of steroids for a long time, they may develop osteoporosis, weight gain, high blood pressure or diabetes.
• Iron overload. This complication is due to the accumulation of iron from blood transfusions. Excess iron can deposit in the heart, liver and endocrine organs such as the pancreas, thyroid gland and gonads. Patients need to take a medication called a chelation medicine that will help them unload the iron.

When should I call my child’s doctor?

You know your child better than anyone else. If you are in doubt or if you have questions or concerns, it is best to contact their pediatrician or other health care professional.

Work closely with your child’s doctor to know what to report. It depends on your child’s age, treatment and other factors. For instance, the clinician will tell you what side effects to watch for if your child is taking a certain medication.