Beta Thalassemia

What is beta thalassemia? Beta thalassemia (pronounced “thal-uh-SEE-me-uh”) is a blood disorder that interferes with your body’s ability to make hemoglobin. Hemoglobin is an iron-rich protein that’s the main ingredient in red blood cells. Hemoglobin enables your red blood cells to carry oxygen to your body’s other cells and tissues. Your cells use the oxygen they receive from red blood cells to make energy. Beta thalassemia is one of two main types of thalassemia. Beta thalassemia and its counterpart, alpha thalassemia, involve gene mutations (or errors) in the hemoglobin protein. This gene mutation disrupts your body’s ability to make a protein in hemoglobin called beta-globin.

How does beta thalassemia affect my body? Low production of beta-globin results in damage to your red blood cells, leading to their removal from blood circulation. If your body can’t make enough new red cells to replace the ones that are lost, anemia develops. Symptoms of anemia occur when there aren’t enough red blood cells to carry oxygen to your body’s tissues causing them to become deprived of oxygen. Anemia symptoms associated with beta thalassemia can range from mild to severe, depending on how low your red blood cell count is.

Who is at risk for beta thalassemia? Beta thalassemia is an inherited genetic disorder. Parents pass along the gene mutation to their biological children. Most people with beta thalassemia live in Africa, the Mediterranean region, the Middle East, India and Southeast Asia. With global migration, cases of beta thalassemia have increased in Northern Europe and North America.

How common is beta thalassemia?

Thalassemia is the most common inherited cause of anemia. Thousands of new beta thalassemia cases are diagnosed each year. Cases have declined as prevention measures, like screenings to identify people who carry thalassemia gene mutations, have increased.

What causes beta thalassemia?

Beta thalassemia results from a mutation (error) that limits beta-globin production in your body. Hemoglobin consists of four protein chains, two alpha-globin chains and two beta-globin chains. Mutations of the alpha-globin chain cause alpha thalassemia, while mutations of the beta-globin chain cause beta thalassemia. A deficiency of either globin chain damages and destroys the red blood cell.

You inherit the gene mutation for beta thalassemia in an autosomal recessive pattern. This happens when both biological parents carry one copy of the mutated gene and one copy of the normal gene. In the most severe form of beta thalassemia, you inherit a copy of the mutated gene from both parents.

In rare instances, inheriting just one mutated beta-globin gene causes beta thalassemia. This is called an autosomal dominant pattern.

What are the types of beta thalassemia?

The number of defective genes you inherit and the mutation’s location will determine your condition’s severity. Some mutations cause no beta-globin to be produced (beta-zero thalassemia). Other mutations cause too little beta-globin to be made (beta-plus thalassemia).

The types of beta thalassemia include the following.

Beta thalassemia major (Cooley’s anemia) is the most severe kind of beta thalassemia. It involves having two missing or defective beta-globin genes. Beta thalassemia major is now known as “transfusion-dependent thalassemia” because people with this condition require lifelong blood transfusions.

Beta thalassemia intermedia may cause mild to moderate anemia symptoms. It also involves having two missing or defective beta-globin genes. You likely won’t need lifelong blood transfusions with beta thalassemia intermedia.

Beta thalassemia minor (beta thalassemia trait) often causes mild anemia symptoms. It involves having one missing or defective beta-globin gene. Some people with beta thalassemia minor don’t have symptoms at all.

What are the symptoms of beta thalassemia?

Your symptoms will depend on how severe your beta thalassemia is. For instance, you may be asymptomatic (no symptoms) or have mild anemia symptoms with beta thalassemia minor. You may have moderate or more severe symptoms with beta thalassemia intermedia and especially beta thalassemia major.

Mild symptoms

Beta thalassemia minor (beta thalassemia trait) is associated with mild anemia symptoms, including:

- Fatigue.

- Dizziness or weakness.

- Frequent headaches.

- Pale skin.

Moderate to severe symptoms

The most severe symptoms are associated with beta thalassemia major. Some of these symptoms also appear with beta thalassemia intermedia, depending on your condition's severity. In addition to experiencing mild symptoms, you may have:

- Shortness of breath with exertion.

- Heart palpitations.

- Yellow skin or whites of your eyes (jaundice).

- Dark or tea-colored urine (pee).

- Slow growth or delayed development.

- Swollen abdomen.

- Weak or misshapen bones in your arms, legs and face.

- Infants with moderate to severe beta thalassemia may be especially fussy and get frequent infections.

How is beta thalassemia diagnosed?

Beta thalassemia is often diagnosed in childhood. Beta thalassemia major, the most severe form, is diagnosed early in childhood, by age 2. Your doctor will diagnose beta thalassemia based on your symptoms and blood test results.

What tests will be done to diagnose beta thalassemia?

Your doctor will diagnose beta thalassemia by performing a simple blood draw and analyzing the sample. Tests may include:

- A complete blood count (CBC): A CBC provides information about your blood cells, including your red blood cells. It can show whether you have too few red blood cells and if they’re smaller than usual, oddly shaped or pale (light red). These characteristics may be signs of thalassemia.

- Reticulocyte count: Immature red blood cells are called reticulocytes. A low reticulocyte count indicates that your body isn’t producing enough red blood cells. Severe thalassemia is usually accompanied by an elevated reticulocyte count. This is because your body is trying to make more red cells to make up for the destruction of the red cells containing the abnormal hemoglobin.

- Molecular genetic testing: Molecular genetic testing allows your doctor to study your hemoglobin closely and identify the mutation associated with beta thalassemia.

- Hemoglobin electrophoresis: A hemoglobin electrophoresis test measures different types of hemoglobin proteins in your blood. Certain types of hemoglobin proteins are increased with beta thalassemia, while other types are decreased.

- Your doctor may perform chorionic villus sampling (CVS) or amniocentesis during pregnancy if there’s a concern that your fetus may carry the mutated gene. CVS tests a portion of the placenta for signs of the gene mutation. The placenta is the organ that allows you and your fetus to share nutrients during pregnancy. Amniocentesis tests the fluid surrounding your fetus for signs of beta thalassemia.

How is beta thalassemia treated?

You’ll likely work with a care team that includes multiple specialists. Working with an experienced hematologist, a specialist who treats blood disorders, is especially important.

Treatments may include:

Blood transfusions: You may need frequent blood transfusions (as much as every two weeks) with beta thalassemia major. During the procedure, you receive blood from a donor. The influx of blood from a transfusion supplies red blood cells needed to carry oxygen to tissues throughout your body.

Iron chelation therapy: Iron is an important part of the hemoglobin protein allowing it to carry oxygen. Too much iron, however, can be harmful. Iron chelation therapy can help prevent iron overload.

Folic acid supplements: Folic acid can help boost your body’s ability to make red blood cells. Your doctor may recommend supplements if you have beta thalassemia minor. You may also take folic acid in addition to receiving regular blood transfusions if your condition is more severe.

Luspatercept: If you have severe thalassemia, you may receive an injection (shot) of luspatercept every three weeks to help your body make more red blood cells. Luspatercept improves anemia in people diagnosed with beta thalassemia who are receiving blood transfusions.

Bone marrow and stem cell transplant: You may receive bone marrow stem cells from a donor. Bone marrow stem cells eventually mature into red blood cells. Replacing your bone marrow stem cells with the stem cells of a healthy donor can cure beta thalassemia. Unfortunately, finding a compatible donor can be a challenge. Also, this type of transplant is considered a high-risk procedure.

What are the complications or potential side effects of treatment?

The most common treatment complication is iron overload. Blood transfusions introduce more red blood cells and iron into your body. After many transfusions, excess iron can accumulate and damage vital organs like your liver, heart and pancreas. Talk with your doctor to determine how frequently you should receive iron chelation therapy to remove excess iron from your body if you’re receiving regular transfusions.

How can I reduce my risk of beta thalassemia?

You can’t reduce your risk of inheriting the gene mutation associated with beta thalassemia. However, you can prevent passing it to your child. Talk to your doctor about screening for beta thalassemia if you or your partner are a potential carrier and considering having a baby.

Is beta thalassemia curable?

The only known cure for beta thalassemia is a bone marrow and stem cell transplant from a compatible donor. Unfortunately, finding a compatible donor is often difficult. Even family members may not be considered compatible donors.

Researchers are currently studying other potential cures for beta thalassemia, such as replacing defective genes with healthy ones (gene therapy). This work is still in its early stages.

What is the life expectancy of someone with beta thalassemia?

Beta thalassemia is treatable. With minor and moderate forms of beta thalassemia, you can expect an average lifespan if you follow your doctor’s treatment guidance. Beta thalassemia major can shorten your lifespan. The most common cause of death is heart failure due to iron overload.

Talk to your doctor about your prognosis based on the severity of your condition.