Thalassemia

What is thalassemia?

Thalassemia (say "thal-uh-SEE-mee-uh") is an inherited blood disorder that causes the body to produce less hemoglobin. Hemoglobin helps red blood cells spread oxygen all through your body. Low levels of hemoglobin may cause anemia, an illness that makes you feel weak and tired. Severe cases of anemia may damage organs and result in death.

What causes thalassemia?

A defect in one or more genes causes thalassemia. It is an inherited blood disorder, passed from parent to child. Both parents must carry a gene for the disease in order to pass it to their child.

What are the types of thalassemia?

Alpha thalassemia and beta thalassemia are the two main types of the disease. Beta is the most common form. A "carrier" has one normal gene and one thalassemia gene in all body cells, a state sometimes called "thalassemia trait." Most carriers lead completely normal, healthy lives.

Beta thalassemia

Beta thalassemia occurs when one or both of the genes that produce beta-globin don't work or only partly work the way they should. People need both alpha- and beta-globin to make hemoglobin. Beta thalassemia mainly affects people from the region around the Mediterranean Sea (such as Greeks and Italians) and, less often, people of African or Asian descent.

There are several subtypes of beta thalassemia. Which type you have depends upon whether one or both genes are affected and whether those genes still produce some working beta-globin.

• If you carry the genetic trait for thalassemia or have one damaged beta-globin gene, you may have mild anemia and probably will not need treatment. This condition is called beta thalassemia minor or beta thalassemia trait. You have thalassemia trait when you inherit a normal gene from one parent and a thalassemia gene from the other.
• When both beta-globin genes are damaged, moderate or severe anemia may develop. In this situation, you have inherited a thalassemia gene from each parent.
  • If you have moderate anemia (beta thalassemia intermedia), you may need blood transfusions. People who have beta thalassemia intermedia usually live into adulthood.
  • People with severe anemia (called beta thalassemia major or Cooley's anemia) usually will not live into adulthood without treatment. Symptoms of anemia usually develop within 6 months of birth.¹ If the child starts receiving blood transfusions early and continues to receive them throughout life, he or she is likely to live longer. Death is usually a result of damage to organs, such as the heart or liver. Lack of oxygen or an iron overload from blood transfusions causes the organ damage.

Alpha thalassemia

Alpha thalassemia occurs when one or more of the four genes that are vital to making hemoglobin are missing or damaged. Alpha thalassemia mainly affects people from southeast Asia, China, and the Philippines, although it occurs in many populations throughout the world. It is sometimes seen in people of African descent.

There are four subtypes of alpha thalassemia. Each type represents the loss of or damage to one, two, three, or four genes.

• One gene: If one alpha-globin gene is missing or damaged, you will have no symptoms and will not need treatment. But you are a silent carrier. This means you don't have the disease but you can pass the defective gene onto your child. Smaller-than-normal blood cells may be the only sign of the condition.
• Two genes: If two alpha-globin genes are missing or damaged, you will have very mild anemia that will not need treatment. This is known as alpha thalassemia minor or alpha thalassemia trait.
• Three genes: If three alpha-globin genes are missing, you will have mild to moderately severe anemia. This is sometimes called hemoglobin H disease, because it produces a heavy hemoglobin. The body removes this heavy hemoglobin faster than it does normal hemoglobin. The more severe forms may need treatment with blood transfusions.
• Four genes: If all four alpha-globin genes are missing (alpha thalassemia major), the fetus will be stillborn or the child will die shortly after birth.¹ The hemoglobin produced by this condition is sometimes called hemoglobin Barts.

What are the symptoms?

Mild thalassemia usually does not cause any symptoms. But symptoms of anemia may develop in more severe forms of the condition and may include:

• Weakness.
• Fatigue.
• Lightheadedness.
• Skin that looks paler than normal.
• Jaundice (skin and whites of the eyes appear yellow).
• Dark urine.
• Decreased appetite and weight loss (poor growth in a child).
• A rapid heartbeat.
• Shortness of breath during exercise.

How is thalassemia diagnosed?

A physical exam and complete medical history are usually the first steps in diagnosing thalassemia. Tests that help confirm a diagnosis of thalassemia include:

• Complete blood count (CBC) and blood smear.
• Gene test.
• Iron level test, to determine whether iron deficiency anemia is present.
• A blood test that measures the amounts of different types of hemoglobin (hemoglobin electrophoresis), to help find out which type of thalassemia you have.
• A complete blood count (CBC) test on other members of your family (parents and siblings), to discover whether they may also have thalassemia.

How is it treated?

Treatment for thalassemia depends on your symptoms.

• Mild thalassemia, the most common form, does not need treatment.
• Moderate thalassemia may be treated with folic acid supplements and blood transfusions.
• Severe thalassemia may be treated with:
  • Blood transfusions.
  • Folic acid.
  • A splenectomy, which is surgical removal of the spleen.
  • A bone marrow transplant, in some severe cases.

Very rare forms of thalassemia may cause organ damage that can result in death. This damage occurs when not enough oxygen reaches the organs. Iron overload also may damage organs, especially the liver. The body can get too much iron through repeated blood transfusions. If this happens, your doctor may give you chelating therapy. Or you may get medicine that binds to the iron in your body and removes it through your urine or stool. You may take this medicine as pill or have it pumped under your skin through a thin tube.

Frequently Asked Questions

Mild thalassemia usually does not cause any symptoms.

People who have more severe forms of the condition may develop symptoms of anemia, which may include:

• Weakness.
• Fatigue.
• Lightheadedness.
• Skin that looks paler than normal.
• Jaundice (skin and whites of the eyes appear yellow).
• Dark urine.
• Decreased appetite and weight loss (poor growth in a child).
• A rapid heartbeat.
• Shortness of breath during exercise.

Less common symptoms of severe thalassemia include:

• Headache.
• Belly pain.
• Ringing in the ears.
• Chest pain.
• A slight fever.
• A sore, smooth tongue.

Children with a more severe form of thalassemia (beta thalassemia major, or Cooley's anemia) usually develop symptoms of anemia within the first few months of life. Paler skin is often the first sign of the disease.² Infants may grow slowly (failure to thrive). Other symptoms may include feeding problems, frequent fevers, and diarrhea. Without early treatment, a child may die or develop severe problems, such as:³

• A deformed face caused by the bone marrow expanding in the bones. This may cause a bulging forehead (frontal bossing).
• An enlarged liver and spleen.
• Brittle, weak bones (most often the long bones in legs and arms and the bones of the spine).

Related problems of severe thalassemia may include:

• Severe bacterial infections. An annual flu shot and the pneumonia vaccine may protect you from severe infections, which can make anemia worse in people with thalassemia.
• Organ damage. Many blood transfusions over time can lead to higher levels of iron stored in the body. The body stores this excess iron in the liver, heart, and other organs. In time, too much iron in these organs (iron overload) may cause damage. To reduce the amount of iron in your body, your doctor may treat you with chelating therapy. Or you may get medicine that binds to the iron in your body and removes it through your urine or stool. You may take this medicine as pill or have it pumped under your skin through a thin tube.

A physical exam and complete medical history are usually the first steps in diagnosing thalassemia. Your medical history includes:

• Your symptoms.
• Your ethnic background.
• The general health of close family members.
• Any other health conditions you may have.
• Any blood tests that you have had.

Results of tests reveal important information, such as the type of thalassemia. Tests that help confirm a diagnosis of thalassemia include:

• Complete blood count (CBC) and blood smear.
  • Blood cells are checked for their shape, color, number, and size. These features help your doctor know whether you have thalassemia and, if so, what type.
  • These tests also tell your doctor if you have mild, moderate, or severe anemia.
• Tests for the genes that often cause thalassemia.
• Blood tests that measure the amount of iron in the blood (iron level tests and a ferritin test).
• A blood test that measures the amounts of different types of hemoglobin (hemoglobin electrophoresis). The results help determine the type of thalassemia you have.
• A complete blood count (CBC) on other members of your family (parents and siblings), to determine whether they have thalassemia.

Doctors often diagnose the most severe form of thalassemia (beta thalassemia major, or Cooley's anemia) within the first year of a child's life.

Treatment for thalassemia depends on the severity of the condition. Thalassemia may be mild, moderate, or severe.

Mild thalassemia is the most common form and does not require treatment.

Moderate thalassemia (thalassemia intermedia and more severe hemoglobin H disease) may be treated with:

• Folic acid (a vitamin that your body needs to produce new red blood cells). People with thalassemia often lack enough folic acid in their diets to keep a good supply of red blood cells.
• Blood transfusions. You may need a blood transfusion when your body is under stress, such as during an infection.

If you have moderate thalassemia, do not take medicines that increase the amount of iron in the body, which can damage organs. These medicines include:

• Iron supplements or multivitamins that contain iron.
• Vitamin C, which can increase the amount of iron that your body absorbs from food.

Severe thalassemia is often treated with:

• Regular blood transfusions. A child with severe thalassemia typically starts to have symptoms when he or she is 6 months old and will need blood transfusions every 4 to 6 weeks. The transfusions often lead to increased iron levels, which also may require treatment.
• Folic acid, which your body needs to produce red blood cells. A person with thalassemia needs folic acid supplements because red blood cells are destroyed faster than normal. As a result, the body often uses up its stores of this vitamin.

Other treatments that doctors consider for severe cases of thalassemia include:

• A splenectomy, which is surgical removal of the spleen.
• In rare cases, a bone marrow transplant. This treatment can cure severe thalassemia, but it must be done before problems related to excess iron stored in the body develop. Phlebotomy, removing blood from the body, is sometimes needed after a successful bone marrow transplant to reduce high iron levels.
• In rare cases, a stem cell transplant.² This procedure involves taking stem cells from the umbilical cord of a newborn. These stem cells are then injected into a child who has severe thalassemia. The donor is most often a brother or sister of the child.

What to Think About

Blood transfusion therapy often creates an excess of iron, which may damage organs if untreated. You may need to use medicines called chelating agents that bind to and remove excess iron from the blood. The chelating agent deferasirox (Exjade) is taken as a pill once a day. The chelating agent deferoxamine mesylate (Desferal) is injected through a tube placed under the skin. A portable pump delivers the medicine in what is usually an all-night procedure. This treatment works best if it is done 5 or 6 nights a week. Both deferoxamine and deferasirox have potentially serious side effects, including hearing loss and kidney, liver, and eye problems.

Researchers are studying how well medicines (hydroxyurea and butyrate) work to get the body to produce fetal hemoglobin in children and adults with thalassemia. Fetal hemoglobin is different than adult hemoglobin. The body does not normally produce it after birth. Fetal hemoglobin may help adult hemoglobin work better in people with thalassemia.⁴

If you have blood transfusions to treat your thalassemia, you need to avoid vitamins that increase iron stored by the body. Excess iron can cause serious damage to your organs. Avoid the following vitamins:

• Multivitamins that contain iron.
• Vitamin C, which can increase the amount of iron you absorb from food.

You may want to get flu shots once a year. Talk to your doctor about getting a pneumonia shot. These shots may protect you from severe infections, which can make anemia worse in people with thalassemia.

It is also important to get help from people who are specially trained in the medical and emotional effects of thalassemia. Talk to your doctor about organizations that can help you cope with the impact this disease has on you and your family.

If you or any of your family members (parents or siblings) have thalassemia or thalassemia trait and you are thinking about having a child, you may want to talk to a health professional who specializes in the study of inherited disorders (genetic counselor) before you become pregnant. A genetic counselor can tell you how likely it is that your child will have thalassemia and how severe it might be.

Organizations

• Blood Transfusion
• Folic Acid Deficiency Anemia
• Iron Deficiency Anemia
• Vitamin B12 Deficiency Anemia

Citations

1. Lo L, Singer ST (2002). Thalassemia: Current approach to an old disease. Pediatric Clinics of North America, 49(6): 1165–1191.

2. Borgna-Pignatti C, Galanello R (2004). Thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis. In JP Greer et al., eds., Wintrobe's Clinical Hematology, vol. 1, pp. 1319–1365. Philadelphia: Lippincott Williams and Wilkins.

3. Weatherall DJ (2006). Disorders of globin synthesis: The thalassemias. In M Lichtman et al., eds., Williams Hematology, 7th ed., pp. 633–666. New York: McGraw-Hill.

4. Vadolas J, et al. (2004). Cellular genomic reporter assays for screening and evaluation of inducers of fetal hemoglobin. Human Molecular Genetics, 13(2): 223–233.

Other Works Consulted

• Hillman RS, Ault KA (2005). Thalassemia. In Hematology in Clinical Practice, 4th ed., pp. 65–79. New York: McGraw-Hill.