What is thalassemia?
Thalassemia is an inherited blood disorder that causes the body to produce less hemoglobin, the protein in red blood cells that helps them carry oxygen from the lungs to all parts of the body. Hemoglobin is made up of four parts: two alpha proteins and two beta proteins. Thalassemia affects one or more of the genes that produce these proteins.
The severity of the disease depends on the type of thalassemia. Children with thalassemia major require ongoing treatment and blood transfusions throughout their lives. In addition, they need ongoing chelation therapy to remove the excess iron that builds up in the blood from these transfusions. Milder forms of thalassemia, including thalassemia intermedia and thalassemia minor, require less aggressive or no treatment at all.
Everyone has four alpha genes and two beta genes that together control the production of hemoglobin. There are three major types of thalassemia, classified based on the severity of symptoms and the genetic defect causing the disease.
What are the types of thalassemia?
Thalassemia minor and silent carriers
Children with thalassemia minor or trait have two alpha genes or one beta gene missing or damaged, while those that are “silent carriers” have one missing or damaged alpha gene. These children do not experience symptoms (except mild anemia in some cases of thalassemia minor), and they do not require treatment.
In children with beta thalassemia intermedia, one or both beta genes are not working properly. They have mild to severe anemia andcan be diagnosed early in childhood or later in life. They may need blood transfusions during pregnancy or when very sick.
Children with thalassemia major need ongoing medical care, including blood transfusions to alleviate severe anemia and chelation therapy to remove excess iron from the blood.There are two subtypes of thalassemia major:
Alpha thalassemia major
- most serious and most rare form of the subtypes of thalassemia
- all four alpha genes are missing
- if untreated, leads to miscarriage or death of the baby shortly after birth
- may be treated with blood transfusions in the womb if discovered early enough in the pregnancy
- babies who survive require lifelong blood transfusions or stem cell transplant and extensive medical care
Beta thalassemia major (also called Cooley’s anemia, after the discoverer)
- neither beta gene is not working properly
- symptoms, which begin during the first year of life, include severe anemia
- monthly blood transfusions needed
- chelation therapy also is needed to remove excess iron that builds up in the body due to frequent blood transfusions
Other types of thalassemia
- Hemoglobin E beta-thalassemia: This form of thalassemia is more common in children of Southeast Asian descent. It results from two separate genetic defects:
- Hemoglobin H disease alpha-thalassemia: This form of thalassemia is most common in Southern China and Southeast Asia. In Hemoglobin H disease:
The defective genes that cause thalassemia are relatively common, especially in people of South Asian, African and Mediterranean descent. However, thalassemia occurs in many populations around the world.
About 300 million people around the world have the “thalassemia trait,” which puts them at risk of having children with some form of thalassemia. More than 1 million people have thalassemia intermedia, while more than 100,000 people have thalassemia major. In the United States, there are only about 1,000 people with thalassemia major.
Hemoglobin H disease and hemoglobin E/beta thalassemia are extremely common in Southern China, and South and Southeast Asia.
How we care for thalassemia
At the Dana-Farber/Boston Children’s Cancer and Blood Disorders Thalassemia Program, our experts provide comprehensive care for children and adults with all forms of thalassemia. For many appointments and certain procedures, your child also can receive care at one of our satellite offices. Treatment for thalassemia depends on the subtype of the disorder, but may include:
- blood transfusions for anemia, based on severity
- regular and comprehensive monitoring for complications of thalassemia and of treatments
- 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)
What is the latest thalassemia research?
We are involved in a number of research initiatives aimed at improving thalassemia care including:
- investigating the effectiveness of new oral iron chelators, drugs that remove excess iron from the body
- improving existing chelation therapies and investigating new ones
- using stem cell transplants to cure patients with transfusion dependent thalassemia
- developing new ways to assess iron levels in the body
- understanding how to use gene therapy to force red blood cells to make a form of hemoglobin called fetal hemoglobin, which our cells make until birth and which is not affected by the genetic defects that cause thalassemia
For many children with rare or hard-to-treat conditions, clinical trials provide new options. Search our open clinical trials.
Thalassemia | Symptoms & Causes
What are the symptoms of thalassemia?
Symptoms of thalassemia depend on the clinical severity of the disease and the therapies employed to treat it. Each child may experience symptoms differently. Patients with thalassemia trait generally do not experience any symptoms.
Transfusion dependent thalassemia
The primary signs and symptoms of Cooley’s anemia in infancy, before diagnosis, are those of severe anemia. Later in childhood and adulthood, transfusion dependent thalassemia symptoms are generally the result of iron overload, a byproduct of the frequent blood transfusions patients with this form of thalassemia require.
Patients with transfusion dependent thalassemia do not typically experience severe anemia once they have started receiving regular transfusion. Without these transfusions, however, they can develop life-threatening anemia.
Symptoms of iron overload may include:
- chronic fatigue
- liver disease
- abdominal pain
- heart problems
- joint pain
Non-transfusion dependent thalassemia
The most common symptoms of non-transfusion dependent thalassemia are related to anemia:
- pale skin, lips, hands or under the eyelids
- increased heart rate (tachycardia)
- breathlessness, or difficulty catching a breath (dyspnea)
- lack of energy, or tiring easily (fatigue)
- dizziness or vertigo, especially upon standing
- irregular menstruation cycles
- absent or delayed menstruation (amenorrhea)
- slow or delayed growth and development
- bony overgrowth or deformities
- an increased risk of bone fractures
What causes thalassemia?
Thalassemia is caused by an abnormality or mutation in the DNA of the cells involved in hemoglobin production. Children inherit this condition from their parents. When one parents is a carrier for thalassemia, a child may develop a form of the condition called thalassemia minor. When both parents are carriers of thalassemia, there is a greater chance their child or children will inherit a more serious form of the condition.
Thalassemia | Diagnosis & Treatments
How is thalassemia diagnosed?
A diagnosis of thalassemia is made after tests to discover which type of thalassemia a child might have. Those tests include:
- a complete blood count (CBC) to measure the number of red blood cells and their concentration of hemoglobin, as well as many other red cell features
- hemoglobin electrophoresis
- genetic tests to identify specific genetic defects that cause thalassemia
After those tests are complete, doctors will be able to outline the best treatment options.
What are the treatment options for thalassemia?
Thalassemia treatment for children requires a multidisciplinary effort, including specialists in hematology and transfusion medicine as well as cardiologists, endocrinologists, gastroenterologists, audiologists, ophthalmologists, infectious disease specialists, geneticists and genetic counselors as necessary.
Treatment for thalassemia depends on the severity of the disorder. If your child has transfusion dependent thalassemia, she will require life-long, ongoing medical care, which may include:
- Blood transfusions from healthy donors, which can alleviate anemia. How often transfusions are necessary will depend on the type of thalassemia. Because of transfusions bring with them the risk of iron overload (which can cause organ damage), children receiving frequent transfusions should be monitored carefully. We use specialized magnetic resonance imaging technologies such as FerriScan and T2* to look for signs of iron overload.
- Iron chelation therapy, which reduces the amount of iron in the body and prevents or treats iron overload.
- Stem cell transplantation to replace the blood-forming stem cells with the defective hemoglobin gene(s). Stem cell transplantation can cure thalassemia by replacing defective blood-forming stem cells with healthy stem cells from a donor. Unfortunately it may not be an option for everyone. The success of a transplant depends on many factors, such as how close the match is between child and donor (matched siblings are best; if your child has a sibling, there is a 1 in 4 chance they will be a match) and the patient's age. The degree to which your child's bone marrow has failed also factors into the discussion whether to pursue a transplant. The decision of whether to proceed with a stem cell transplant should be discussed with your child’s hematologist and a stem cell transplant team.
In general, children with non-transfusion dependent thalassemia experience less severe symptoms. They need regular medical follow-up, but may not require frequent blood transfusions.
What’s the long-term outlook for children with thalassemia?
In the past, patients with transfusion dependent thalassemia had a significantly reduced life expectancy. Today, however, thanks to blood transfusion therapy and effective iron chelators, the life expectancy for children with severe thalassemia is constantly improving. Once rare, survival to older adulthood is becoming the norm.