What Is Thalassemia?
Thalassemia is an inherited blood disorder that causes the body to produce less hemoglobin than normal. Hemoglobin is a protein in red blood cells that helps deliver oxygen throughout the body. When hemoglobin levels are low, red blood cells cannot carry enough oxygen to the body. This can cause mild or severe anemia depending on how many genes are affected. Anemia can make a person feel tired, weak, lightheaded, and short of breath.
Thalassemia can come in different forms depending on which hemoglobin gene is missing or not working correctly. There are two types of thalassemia.
Alpha Thalassemia
We inherit four alpha-globin genes from our parents, two from each parent. These genes create the alpha hemoglobin chain, a building block of hemoglobin.
- Alpha thalassemia minor, also called alpha thalassemia trait, develops when one or two alpha-globin genes are missing or abnormal.
- Hemoglobin H disease, or alpha thalassemia, develops when three alpha-globin genes are missing or abnormal.
- Hemoglobin Barts disease, or alpha thalassemia major, develops when four alpha-globin genes are missing or abnormal.
Beta Thalassemia
We also inherit two beta-globin genes, one from each parent. These two genes make the beta hemoglobin chain, another component of hemoglobin.
- Beta thalassemia minor, also called beta thalassemia trait, develops when one beta-globin gene is missing or abnormal.
- Beta thalassemia intermedia or beta thalassemia major develops when both beta-globin genes are missing or abnormal.
The severity of these conditions depends on how many abnormal genes a person inherits and whether the genes have some function or none at all.
What Causes Thalassemia?
Thalassemia is caused by defective genes that affect hemoglobin production. These mutated genes are passed from parents to their biological children.
Who Is at Risk for Thalassemia?
Thalassemia is a genetic condition passed down from one or both biological parents with a genetic mutation. It is common in those of Southeast Asian, African, and Mediterranean descent.
What Are the Symptoms of Thalassemia?
There are three basic severities of thalassemia:
- Minor or trait, which is asymptomatic and does not require therapy
- Thalassemia intermedia, which is associated with anemia and may not require treatment until adulthood
- Thalassemia major, which requires treatment from early childhood
Thalassemia symptoms depend on the severity and type of condition. Since thalassemia causes the body to produce less red blood cells, symptoms of a low blood count, or anemia, are common. These symptoms include:
- Weakness
- Fatigue
- Dizziness
- Increased heart rate
- Shortness of breath
For patients with thalassemia, their red blood cells live for a shorter time than healthy red blood cells. The increased breakdown of shorter-lived red blood cells can lead to symptoms and long-term complications, such as:
- Pale or yellowish skin
- High blood pressure in the arteries between the heart and lungs
- Open leg wounds between the knee and ankle
The most common complication of moderate-to-severe thalassemia is iron overload. The body accumulates too much iron, either from the disease itself or treatment with many blood transfusions. Increased levels of iron can cause damage to the liver, heart, and endocrine system, which includes hormone-producing glands that control processes throughout the body.
In thalassemia major, additional complications can occur:
- Facial bone deformities
- Delayed growth
- Heart problems
- Enlarged spleen
How Is Thalassemia Diagnosed?
People with moderate to severe thalassemia often have symptoms in the first years of life and are diagnosed as children. Several tests are used to diagnose thalassemia, including:
- Complete blood count (CBC) to check hemoglobin levels and the size and number of red blood cells.
- Hemoglobin electrophoresis to measure the type and amount of hemoglobin in the body.
- Genetic tests to identify genetic defects that cause thalassemia.
Prenatal testing may also be done before a baby is born to determine the presence and severity of thalassemia. These tests include:
- Chorionic villus sampling involves removing a piece of the placenta for evaluation during the 11th week of pregnancy.
- Amniocentesis examines a sample of the fluid that surrounds the fetus during the 16th week of pregnancy.
How Is Thalassemia in Children Treated?
Pediatric patients receive care through Dana-Farber/Boston Children’s Cancer and Blood Disorder Center. At the Dana-Farber/Boston Children's Thalassemia Program, our experts provide comprehensive care for all forms of thalassemia. Treatment for thalassemia depends on the subtype, but may include:
- Blood transfusions for anemia
- Regular and comprehensive monitoring for complications of thalassemia and its treatment
- Iron chelation therapy, to remove excess iron from the body
- For certain cases, stem cell transplantation to replace the blood-forming stem cells with the defective hemoglobin gene(s)
- Gene therapy for patients 12 years and older with transfusion-dependent beta thalassemia
Learn more about thalassemia in children on the Boston Children's Hospital website.
How Is Thalassemia in Adults Treated?
Thalassemia treatment depends on the severity of the condition. Thalassemia minor requires no treatment. Patients with other forms of thalassemia have several treatment options tailored to their symptoms and complications:
- Regular blood transfusions to increase red blood cells within the body.
- Chelation therapy to remove excess iron from the blood due to frequent blood transfusions.
- Use of luspatercept, a medication to raise hemoglobin levels or reduce transfusion needs in beta thalassemia.
- Use of hydroxyurea, a medication to make the body switch to a different type of hemoglobin and is used for some beta thalassemia subtypes.
Stem cell transplant and gene therapy offer the possibility of a cure for thalassemia.
Stem Cell Transplant for Thalassemia
A bone marrow/stem cell transplant is a potentially curative treatment for patients with thalassemia. A stem cell transplant relies on a donor to provide stem cells that can produce healthy blood cells and immune system. The donor can be a family member or an unrelated donor identified through international registries.
Learn more about stem cell transplantation in adults.
Gene Therapy for Thalassemia
Gene therapy is a way of treating disease by changing the genetic instructions within an individual’s cells. When a gene is missing or doesn’t work correctly, it can cause disease in the body. Gene therapy aims to fix the faulty or missing gene to treat a disease.
Gene therapy for thalassemia is a complex and lengthy treatment process that alters genes in a patient’s stem cells to produce a form of hemoglobin that allows for more effective oxygen delivery to the body. By improving oxygen delivery to the body, gene therapy reduces or eliminates the need for blood transfusions for patients with thalassemia.
Gene therapy is FDA-approved for patients 12 years and older with transfusion-dependent beta thalassemia.
Learn more about gene therapy in adults.
Young adults may be evaluated at the Dana-Farber/Boston Children's Gene Therapy Program.