Diamond-Blackfan Anemia: What to Know

Diamond-Blackfan anemia (DBA) is a rare blood disorder that causes a lack of healthy red blood cells (anemia). Red blood cells bring oxygen to your body’s tissues and organs, which is vital for cell survival. In the case of DBA, the bone marrow doesn’t make enough healthy red blood cells to meet the body’s needs. 

A genetic change typically causes DBA. A little less than half of the time, this change is inherited from one parent. In other cases, it is a sporadic mutation that first appears in the affected person.

DBA is usually diagnosed in infancy—in the first few months of life. It affects 5 to 7 out of every 1 million births. About 30 people are born with DBA each year in the United States and 5,000 worldwide.

The genetic changes that lead to DBA also cause other physical effects on various body parts and systems, including an increased risk of certain cancers. DBA is also known as congenital pure red cell aplasia, Aase syndrome, erythrogenesis imperfecta, congenital hypoplastic anemia, or inherited erythroblastopenia.

This article will cover Diamond-Blackfan anemia's life expectancy, signs, symptoms, treatments and cures, and physical effects of the disease and its treatments. 

What Causes Diamond-Blackfan Anemia?

The specific mechanisms that cause Diamond-Blackfan anemia are still being researched. Generally, genetic changes to the proteins that code for the body's ribosomes—the protein-making factories of the cells—lead to a malfunction in the body's bone marrow. 

Research suggests that when there aren't enough ribosomes, or the ribosomes aren't working right, they lead to the self-destruction of blood-forming cells in the bone marrow. The bone marrow fails to make enough red blood cells, which carry oxygen to the body's tissues, causing anemia.

In most cases of DBA—about 80% to 85%—the change is in one of several known genes. Specifically, 25% are changes in the RPS19 gene. Another 25% to 35% are changes in the RPL5, RPL11, RPL35A, RPS10, RPS17, RPS24, or RPS26 genes.

Others have rare genetic changes in proteins associated with ribosomes. Around 10% to 15% of people diagnosed with DBA do not have a specific gene change thought to be causing the disorder.

Symptoms of DBA

The symptoms of Diamond-Blackfan anemia vary from person to person. Even within families with the same gene change, some people may have mild symptoms while others are more severe.

A mild form of DBA may mean mild or no anemia, with only slight changes to the red blood cells or some minor physical changes. A severe form of DBA may cause uncontrollable anemia and be fatal. Severe symptoms require immediate and ongoing medical care, while mild symptoms may not.

The most apparent sign of DBA is anemia. Symptoms of anemia include:

• Fatigue
• Weakness
• A pale appearance
• Rapid heartbeat
• Irritability
• Poor appetite

About half of people with DBA have these physical differences, which can be mild or more obvious. Many of these physical differences are present at birth. They include:

• Unique facial features that include wide-set eyes, droopy eyelids, a broad, flat nose bridge, small, low-set ears, a small lower jaw, a cleft palate, or a cleft lip
• Eye problems that include cataracts (clouding of the lens of the eye), increased eye pressure (glaucoma), or crossed eyes
• A small head with a low hairline and a short, webbed neck
• Shoulder blades that are smaller and higher than usual
• Malformed or absent thumbs
• Slow growth, leading to short stature, which is more obvious as they grow in 30% of people with DBA
• Kidney abnormalities
• Heart issues
• Changes with the urogenital tract—the opening of the urethra may be on the underside of the penis

How Is DBA Diagnosed?

About 90% of people with Diamond-Blackfan anemia are diagnosed in the first year of life, generally by 4 months of age.

The process typically starts when the child fails to thrive and is very pale. Anemia is diagnosed, then the healthcare providers start to search for a cause. To diagnose DBA, healthcare providers will do a variety of tests. These include:

• Complete blood count (CBC) tests to assess red blood cells, white blood cells, and platelets in a blood sample and measure mean corpuscular volume (MCV, the average size of the red blood cells), which is typically high in DBA.
• Reticulocyte count blood tests to count the number of immature or young red blood cells in a sample
  
• Erythrocyte adenosine deaminase (eADA) activity levels, which is elevated in 80% to 85% of people with DBA
• Genetic testing to find a gene change linked to DBA

What Are the Complications of DBA?

The complications of Diamond-Blackfan anemia include an increased risk of cancer and blood disorders and fertility implications. 

Bone marrow malfunction in DBA can cause a disorder in which immature blood cells fail to develop into healthy, mature blood cells. This is called myelodysplastic syndrome and is considered preleukemic because it can lead to cancer of the white blood cells.

This puts people with DBA at an increased risk of developing acute myeloid leukemia (AML). They also have a higher risk of other cancers at a young age. These include bone cancer (osteosarcoma), colon cancer, and cancers of the female urogenital system. About 13.7% of people with DBA get cancer by age 45.

In addition to cancers, women with DBA may have delayed puberty, irregular menstrual cycles, decreased fertility, and a high risk of miscarriage. (Note that the terms for sex or gender from the cited sources are used.)

Is DBA a Fatal Illness?

Yes, DBA can be deadly. There are also complications of this disorder, like cancer, that can kill. Complications and side effects of treatment, including iron overload, are common causes of death in people with DBA.

Causes of death for people with DBA include:

• Infections due to a weakened immune system
• Complications from a peripherally inserted central catheter (PICC) line or port used for transfusions
• Iron overload from blood transfusions
• Complications of stem cell transplant 
• Cancer
• Hydrops fetalis, a complication that happens to babies born severely anemic
• Aplastic anemia, a low count of all blood cells, including red blood cells, white blood cells, and platelets

Is There a Cure for DBA?

A hematopoietic stem cell transplant can cure Diamond-Blackfan anemia. But it comes with a host of issues and complications that can be fatal, and there is always a possibility of spontaneous recurrence of the anemia after the transplant.

The best candidates for stem cell transplants include those who do not react well to current treatments and are dependent on red blood cell transfusions. However, these transfusions overload their system with iron, which can lead to worse outcomes.

The people who do the best with stem cell transplants are children under 10 years old. Studies have shown they have a five-year survival of 86.6%.

Stem cell transplant complications are one of the leading ways that people with DBA die. People with DBA who get stem cell transplants are at risk of:

• Severe graft-versus-host disease, in which the cells from the donor launch an immune attack on the recipient
• Infections
• Fertility issues 
• Cancer 

Other DBA Treatments

There are two major ways to treat DBA besides a stem cell transplant. 

The first and best treatment option is glucocorticoid, for example, prednisone. This treatment improves anemia in about 80% of people with DBA. These drugs are often started at a high dose for about four weeks, then tapered to the lowest active dose possible to reduce side effects. 

If the glucocorticoids don’t work, need to be administered at too high of a level, or the side effects are unmanageable, the best treatment option is to get a regular red blood cell transfusion every three to five weeks. Once the anemia is resolved, the interval of continued transfusions is determined based on a person’s growth, brain development, and how the patient is doing.

People may also get red blood cell transfusions if they’re eligible for a stem cell transplant but haven’t found a donor yet, or if they need a break from the glucocorticoids due to side effects. Red blood cell transfusions can be combined with low doses of glucocorticoids.

Side Effects From DBA Treatment

Both glucocorticoids and red blood cell transfusions have substantial side effects and long-term complications. 

Glucocorticoid Side Effects

When people take glucocorticoids for a long time, they can often have complications and side effects. These include:

• Cataracts that cloud the eyes or increased eye pressure (glaucoma)
• Osteoporosis, which weakens the bones and can lead to avascular necrosis, in which the bone tissue dies away
• At high risk for infections, including pneumonia (lung infection) 
• Further-impaired growth 
• Addison's disease, or not enough of certain steroid hormones 
• Diabetes, which is the disruption of normal blood sugar levels
• Delayed puberty and impaired pubertal progression
• Weight gain
• High blood pressure
• Stomach and intestinal ulcers 

Blood Transfusion Side Effects

Prolonged red blood cell transfusions can lead to iron buildup in the body. Iron overload in the heart, liver, and endocrine organs can lead to:

• Abnormal heart rhythms
• Congestive heart failure
• Liver scarring
• Diabetes
• An underactive thyroid gland
• Menstrual problems and disorders of the testes

Transfusion-associated iron overload is one of the leading causes of death for people with DBA. People dependent on transfusions require iron chelation therapy every 10 to 12 transfusions to avoid iron toxicity.

DBA and Children

About 90% of DBA diagnoses are made in babies in their first year of life. Infants diagnosed with DBA first get red blood cell transfusions until 1 year old. Healthcare providers then test glucocorticoids to determine how well they prevent anemia.

Since all of these treatment options have their complications and side effects, the best thing you can do for your child is advocate for them. Talk with their healthcare provider if they have challenges with the process or side effects. Ask about clinical trials or other treatment options.

Children under age 10 have the best outcomes for stem cell transplants, so discuss that option with your healthcare provider if your child is transfusion-dependent.

Can You Reduce the Risk of Passing DBA to Your Children?

Most cases of DBA are due to specific genetic changes. These genetic changes can be passed down from parent to child. If a person’s genome has just one altered gene, that’s enough to cause the disorder. In about 45% of cases, the person with DBA has inherited the mutation from a parent, while in others, the change first occurred in the affected person and was not inherited.

If you have one of the major genetic mutations that cause DBA, the risk of passing the condition on to your child is 50%. If you have DBA and the mutation has been identified as the cause, you can visit a fertility specialist for information on how to conceive a child without the mutation by using preimplantation genetic testing.

If you’ve already conceived a child, they either have the mutation or don’t. Prenatal genetic testing can tell you if the fetus has the mutation.

How Long Can You Live With DBA?

Interestingly, DBA can go into remission (get better) spontaneously. But it can also come back at any time.

Many people with DBA can live long, full lives, depending on the severity of their case and the response to treatments and side effects. About 75% of people with DBA survive to age 50. At age 30, about 13% of people with DBA will have died. By age 45, 23% will have died of complications of DBA or treatments.

How to Take Care of Yourself With DBA

If you have DBA, you’ll likely have a team of healthcare providers tracking your health. You’ll get CBCs several times a year.

If anything changes, you’ll need a bone marrow test to check the status of your blood-making cells. These tests will check for genetic changes that might indicate you’re developing myelodysplastic syndrome or leukemia.

If you‘re taking glucocorticoids, your healthcare providers will watch your blood pressure and (in children) growth. People getting regular transfusions will have an endocrinologist monitoring their iron levels. 

Living with DBA isn’t easy. It can help to keep your stress levels low, embrace healthy habits, and find support locally or through online groups for people with DBA or rare diseases. Talk to a genetic counselor about your risk of passing your disease on. 

Whether you’re on glucocorticoids or not, avoid getting an infection—wash your hands regularly, wear a mask, and stay away from large gatherings and sick people. 

As you age, talk to your healthcare provider about when you should start getting cancer screenings.  

Summary

Diamond-Blackfan anemia (DBA) is a rare blood disorder. It causes a lack of red blood cells, called anemia. Genetic changes typically cause it. These changes also cause physical changes and an increased risk of certain cancers.

Symptoms of DBA can vary from mild to severe. They may include fatigue, weakness, pale appearance, rapid heartbeat, irritability, and poor appetite. DBA physical differences include facial features, eye problems, and developmental abnormalities.

Tests used to diagnose DBA include blood and bone marrow tests and genetic testing. The disorder can be life-threatening. Complications include cancer, infections, and iron overload from blood transfusions.

Stem cell transplant can cure DBA, but it comes with significant risks. Other treatment options include glucocorticoids and regular red blood cell transfusions. Both treatments have side effects and long-term complications.

Living with DBA requires regular medical monitoring. The life expectancy of individuals with DBA varies. Many people with DBA live long, whole lives.