What Is Diamond-Blackfan Anemia? Symptoms, Causes, Treatment

This article explores Diamond-Blackfan anemia (DBA), an uncommon blood condition. Find out about the condition, what causes it, the symptoms that can occur, and how it is managed throughout a person’s lifetime.

What is Diamond-Blackfan anemia?

Diamond-Blackfan anemia (DBA) is a type of anemia, also known as pure hereditary red cell aplasia.¹

DBA is hallmarked by genetic mutations. It develops when the bone marrow cannot produce enough red blood cells. The bone marrow in the body makes new blood cells, such as red blood cells, white blood cells, and platelets. In DBA, the bone marrow cannot produce enough red blood cells to fulfill the body’s needs.

The condition typically manifests in infancy, during the first year of life. About half of cases are familial and the rest are thought to occur sporadically.²

Most people affected have physical anomalies linked to DBA. The condition’s physical signs and symptoms can differ from person to person.³

Signs and symptoms of DBA

The signs and symptoms of this form of anemia can manifest in many parts of the body, and some symptoms occur more often than others.⁴

Frequent signs and symptoms include the following:

• Progressive anemia

• Abnormality of the head

• Erythroid hypoplasia

• Growth delay

• Lethargy

• Abnormally pale skin

• Low birth weight or small size for gestational age

Less common signs and symptoms include the following:

• Structural anomaly of the heart

• Abnormalities in the upper arm or hand

• Missing or short thumb

• Sprengel deformity (a rare congenital condition where one shoulder blade is higher than the other)

• Horseshoe kidney

• Neurodevelopmental delay

• Turner syndrome-like appearance (webbed neck, low hairline, small chin and jaw, high-arched palate, and a broad chest with wide-spaced nipples)

• Short stature

What’s the difference between Fanconi anemia and Diamond-Blackfan anemia?

Fanconi anemia (FA) is an uncommon genetic condition caused by pathogenic mutations. The mutations occur in any of the genes involved in the DNA repair pathway (there are over 22). It’s the most common hereditary reason for bone marrow failure.⁵

Fanconi anemia is typically hallmarked by cytopenias (deficiencies in different blood cells such as red blood cells and thrombocytes), increased cancer risk, and congenital and developmental anemias.

FA is typically on a scale. Some patients may have mild cytopenias for years before receiving a diagnosis.

When considering the difference between Diamond-Blackfan anemia and Fanconi anemia, several characteristics set them apart. Genomic instability and bone marrow failure in FA are unlike those linked to DBA symptoms.

What causes Diamond-Blackfan anemia?

About 40–45% of people with DBA inherit altered genes from their biological parents. However, there’s typically a wide range of severity within a family.⁶

Mutations in over 20 genes are able to cause DBA, including the RPL5, RPL11, RPL35A, RPS10, RPS17, RPS19, RPS24, and RPS26 genes. These and other DBA-related genes give instructions for constructing ribosomal proteins, which are parts of cellular structures called ribosomes. Ribosomes process the genetic instructions inside the cell to produce proteins.⁷

Who is at risk of Diamond-Blackfan anemia?

Diamond-Blackfan anemia is very rare. According to many studies, it occurs 1–4 times per 500,000 live births. Another set of analyses suggests it occurs in about 5 in 1 million live births.⁸ ⁹

Children who inherit a dominant variation of DBA often develop the condition. However, it may affect them less or more severely than it did their parents.¹⁰

How is Diamond-Blackfan anemia diagnosed?

Medical professionals may use several tests to diagnose this condition.¹¹

• Complete blood count (CBC) with reticulocytes: DBA will show low hemoglobin and reduced red blood cells and reticulocytes (immature blood cells).

• Bone marrow aspiration and biopsy: This procedure involves an examination of bone marrow samples.

• Genetic testing: These tests can detect a gene mutation in some people with DBA.

• Specialized blood tests: High erythrocyte adenosine deaminase activity level (eADA) and fetal hemoglobin level (HbF) can indicate DBA.

How is DBA treated?

Treatment options for Diamond-Blackfan anemia include corticosteroids, chronic (regular) red blood cell transfusions, and hematopoietic stem cell transplantation.¹²

• Corticosteroids: These drugs encourage the production of extra red blood cells in the bone marrow. The response rate ranges from 50–75%.¹³

• Chronic red cell transfusion: Regular blood transfusions can boost hemoglobin levels to support healthy growth and development. Iron chelation therapy is also common to avoid excessive iron accumulation. Iron levels can build up because of chronic transfusions. Iron chelation removes iron from the blood with special drugs, preventing fatal damage to the heart and liver.

• Hematopoietic stem cell transplantation (HSCT): HSCT, commonly called bone marrow transplant, is most successful with sibling donors, particularly in those aged nine years or younger.

What is the prognosis for Diamond-Blackfan anemia?

Diamond–Blackfan anemia has a wide range of symptoms. This diversity makes it challenging for medical professionals to predict an individual’s prognosis. Some people with DBA may have minor medical issues that have no impact on their lifespan. Others may experience more severe symptoms or significant illnesses, including potentially fatal heart or renal problems.

A potential complication of DBA is a higher potential for cancer diagnosis. These cancers include acute myelogenous leukemia, colon cancer, and osteogenic sarcoma.¹⁴

An individual with DBA also has increased risk of developing myelodysplastic syndrome. This is a pre-leukemic condition where the bone marrow cannot produce healthy blood cells.¹⁵

Severe anemia or other conditions may affect the average lifespan of people with DBA. The condition is treatable because it often responds to steroids, and red blood cell transfusions are relatively easy to administer. About 20% of patients enter stable remission by age 25.¹⁶

The lowdown

Diamond-Blackfan anemia occurs when the bone marrow cannot create enough red blood cells. It’s often diagnosed within the first year of life but can be misdiagnosed until adulthood. Around half of cases are inherited. The other half occur sporadically.

Fatigue, pure red cell aplasia, lethargy, pallor, and developmental delay are just some of the signs and symptoms of DBA.

Corticosteroid medication, chronic blood transfusion, and bone marrow transplant are the three main treatment options for the condition.