Thalassemia is a general name for a group of inherited blood diseases. They involve abnormalities in hemoglobin, the oxygen-carrying part of the red blood cells. Hemoglobin is mainly made up of two kinds of protein, called alpha and beta globin. Individuals with thalassemia do not produce enough of one (or occasionally both) of these proteins. As a result, their red blood cells may be abnormal and unable to carry enough oxygen throughout the body.
The two main types of thalassemia are called alpha and beta thalassemia. Individuals with alpha thalassemia do not produce enough alpha globin, and those with beta thalassemia lack sufficient beta globin. There are a number of different forms of alpha and beta thalassemias, with symptoms ranging from mild to severe.
Thalassemia is among the most common inherited disorders caused by a single abnormal gene. More than 100,000 babies worldwide are born each year with severe forms of thalassemia, according to the National Academy of Sciences (1). Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry.
What is alpha thalassemia?
There are at least five main types of alpha thalassemia. These are most common in people of Southeast Asian, Indian, southern Chinese, Middle Eastern, and African ancestry (2). There are four genes that control the production of alpha globin. The severity of the condition is determined by how many of these genes are missing or abnormal.
- Silent carrier, the mildest form, has one alpha globin gene missing or abnormal. Affected individuals generally have no symptoms, but they can pass on the genetic abnormality to their children.
- Alpha thalassemia minor, in which two alpha globin genes are missing or abnormal, usually does not cause major health problems. However, affected individuals may have mild anemia and can pass the condition on to their children.
- Hemoglobin H disease is caused by having only one normal alpha globin gene. The condition results in abnormalities in the red blood cells and rapid destruction of these cells. Most affected individuals have mild to moderate anemia and can live fairly normal lives. The anemia may temporarily worsen when the individual has a viral infection or when they are treated with certain medications (such as sulfa drugs) (3). Some affected individuals eventually develop complications, such as an enlarged spleen and gallstones (3). Individuals with hemoglobin H disease should receive regular medical care to detect and treat these complications. Some may need occasional blood transfusions (4).
- Hemoglobin H-Constant Spring is a more severe form of hemoglobin H disease. Affected individuals have one normal alpha globin gene, plus one abnormal one that carries a specific mutation (change) called Constant Spring. Those with this condition generally have moderate to severe anemia and often develop complications, such as an enlarged spleen. Some need blood transfusions from time to time, such as when they develop an illness with a fever, while others need more frequent transfusions (3, 4).
- Alpha thalassemia major, the most severe form, results from having no genes for the production of alpha globin. Affected fetuses suffer from severe anemia, heart failure and fluid buildup. They usually are stillborn, but some die in the first hours after birth. In rare cases, babies diagnosed and treated before birth with blood transfusions have survived. These babies require lifelong blood transfusions (4).
What is beta thalassemia?
There are three main forms of beta thalassemia, which range from having no effect on health to having severe health effects. These are most likely to affect people of Greek, Italian, Middle Eastern, Southeast Asian, southern Chinese and African descent (2). Two genes control the production of beta globin, and mutations (changes) on one or both of them can cause the disorder.
- Thalassemia minor (also called thalassemia trait) usually causes no symptoms, but mild anemia and other changes in the blood do occur.
- Thalassemia intermedia usually results in a mild to moderate anemia, though severity varies greatly (5). Affected children may develop some of the complications seen in thalassemia major, including poor growth and bone abnormalities (including fractures). Many affected individuals require occasional or more frequent blood transfusions to reduce complications (2, 5)
- Thalassemia major is the most severe form. It also is called Cooley's anemia, named after the doctor who first described it in 1925. Most affected children appear healthy at birth. However, during the first year or two of life, they become pale and fussy and have a poor appetite. They grow slowly and often develop jaundice (yellowing of the eyes and skin). Without treatment, they develop an enlarged spleen and liver, thinning bones that break easily, abnormal facial bones, frequent infections, and heart problems, and they die in the first decade of life. Affected children require regular blood transfusions beginning in infancy, which allows normal growth and development (5).
Other forms of thalassemia related to beta thalassemia are E-beta thalassemia and Hb S/beta thalassemia. E-beta thalassemia is most common in people from Cambodia, Vietnam, Thailand and Laos (4). Individuals with E-beta thalassemia produce a variant form of hemoglobin called hemoglobin E. Individuals who produce hemoglobin E generally are healthy or have only a mild anemia, unless they also have a form of beta thalassemia. They are then said to have E-beta thalassemia. This condition results in mild to severe anemia. Some affected individuals have symptoms resembling beta thalassemia intermedia, while others have more severe symptoms resembling beta thalassemia major (4).
Individuals with Hb S/beta thalassemia inherit one gene for beta thalassemia and one gene for sickle cell disease, another inherited anemia. Symptoms generally resemble those of sickle cell disease, including varying degrees of anemia, serious infections, pain and damage to vital organs. Often, symptoms are milder than for sickle cell disease, though severity varies.
What is the treatment for thalassemia?
Blood transfusions are used to treat severe forms of thalassemia. Children and adults with beta thalassemia major require regular transfusions. Some individuals with beta thalassemia intermedia, E-beta thalassemia, and hemoglobin H-Constant Spring require tranfusions from time to time, or sometimes more frequently. Some may need a transfusion if they develop a viral illness or other infection, which may cause anemia to become more severe. More frequent transfusions may be recommended if these individuals develop complications.
Children with severe thalassemia, such as beta thalassemia major, generally receive a transfusion every 2 to 3 weeks (2). Regular transfusions help keep hemoglobin levels near normal and help prevent many of the complications of thalassemia. This treatment improves the child's growth and well-being and usually prevents heart failure and bone deformities.
Unfortunately, repeated blood transfusions lead to a buildup of iron in the body. Iron buildup can damage the heart, liver and other organs. To help prevent organ damage, children and adults who receive regular transfusions are treated with a type of drug called an iron chelator. This drug binds to iron and helps the body get rid of excess iron.
Until recently, the only drug approved in the United States to prevent iron buildup was deferoxamine (Desferal or DFO). Individuals usually receive this drug over 6 to 8 hours, often while they are sleeping, five to seven nights a week. The drug is delivered by a pump under the skin (2). In November 2005, the U.S. Food and Drug Administration (FDA) approved the first oral iron chelating drug (Exjade or deferasirox) (6). This oral drug, used alone or in combination with deferoxamine, may simplify treatment for affected children and adults.
Individuals with beta thalassemia major who are treated with regular blood transfusions and iron chelation often live 40 years or longer (1). The most common cause of death in these individuals is heart complications caused by iron buildup (1).
Children and adults with thalassemia must undergo tests to measure the level of iron in their bodies. Blood tests are used to measure the amount of iron in the blood. Unfortunately, blood tests are not very accurate in measuring the levels of iron in the heart and liver. Doctors may recommend a yearly liver biopsy, a surgical procedure in which a small amount of liver tissue is removed and tested. A few medical centers have begun to use new noninvasive imaging tests called SQUID and T2* to measure iron levels in the liver and heart (1, 2, 5). For more information on where these tests are available, contact the Cooley's Anemia Foundation at firstname.lastname@example.org.
Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available (2, 7). Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 80 percent of children who have a fully matched family donor (7). However, only about 20 to 30 percent of children with thalassemia have a family member who is a suitable donor (7). The procedure is risky and can result in death. Scientists are evaluating whether a transplant using umbilical cord blood (which, like bone marrow, contains unspecialized cells called stem cells that produce all other blood cells) from a newborn sibling may be as effective as a bone marrow transplant, while posing fewer risks.
How is the disease transmitted?
All forms of thalassemia are inherited. The disease cannot be caught from another person who has it. Thalassemia is passed on through parents who carry the thalassemia genes in their cells.
When both parents carry alpha thalassemia genes, any child that they have is at risk for inheriting a more severe form of this condition. Individuals who know they have one of these disorders, those with family histories of these disorders, and those from countries where they are common should consider consulting a genetic counselor to find out whether their children could be at risk. (Health care providers can provide referrals to genetic counselors, or individuals can find them by contacting a major medical center.)
When two individuals with beta thalassemia trait have children together, there is a 25 percent chance (1 in 4) that any child they have will inherit a thalassemia gene from each parent and have a severe form of the disease. There is a 50 percent (2 in 4) chance that the child will inherit one of each kind of gene and have the trait like its parents; and a 25 percent (1 in 4) chance that the child will inherit two normal genes and be completely free of the disease. The odds are the same for each pregnancy when both parents have the beta thalassemia trait.
Women with milder forms of thalassemia usually have healthy pregnancies. Until recently, pregnancy was rare in women with beta thalassemia major. Several recent studies suggest that pregnancy appears safe for a woman with well-treated beta thalassemia major who does not have heart problems (8). As long as her partner does not carry a gene for thalassemia, her children will not be at risk for thalassemia, although all will be carriers (thalassemia minor).
Is there a test for thalassemia?
Yes. Blood tests and family genetic studies can show whether an individual has any form of thalassemia or thalassemia trait. Newborn screening tests now identify many babies with thalassemia. In addition, prenatal testing using chorionic villus sampling (CVS) or amniocentesis can detect or rule out thalassemia in the fetus. Researchers are seeking to develop noninvasive prenatal tests the look at fetal DNA (genetic material) in the mother's blood.
What research on thalassemia is taking place?
Scientists are working on better ways to remove excess iron from the body to prevent or delay iron overload. They are developing and testing new oral iron-chelating drugs and looking at whether combining one of these drugs with deferoxamine may be more effective than either treatment alone (1, 5).
Researchers are studying the effectiveness of certain drugs (including hydroxyurea, a drug used to treat another inherited anemia called sickle cell disease) in reactivating the patient's genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth. After birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of patients with beta thalassemia produce more fetal hemoglobin to make up for their deficiency of adult hemoglobin. Studies to date suggest that treatment with these drugs may be helpful for some patients with beta thalassemia intermedia (1).
Researchers also are exploring the possibility that dietary treatments, such as with vitamin E, may help reduce organ damage from iron buildup (4, 5). Others continue to improve bone marrow transplantation methods that may offer a cure to more children with thalassemia.
March of Dimes grantees have been among the many scientists seeking to develop an effective form of gene therapy that may offer a cure for thalassemia. Gene therapy may involve inserting a normal alpha or beta globin gene into the patient's stem cells, possibly allowing these immature blood cells to produce normal red blood cells.
For more information
Cooley's Anemia Foundation
129-09 26th Avenue, #203
Flushing, NY 11354
1. National Academy of Sciences. Cooley's Anemia Eighth Symposium. Posted 7/22/05.
2. Cooley's Anemia Foundation. About Thalassemia. Accessed 9/15/05..
3. Northern California Comprehensive Thalassemia Center. Alpha Thalassemia. Accessed 9/16/05.
4. Cohen, A.R., et al. Thalassemia. Hematology 2004, American Society of Hematology, pages 14-34.
5. Rund, D. and Rachmilewitz, E. Medical Progress: Beta-Thalassemia, New England Journal of Medicine, volume 353, number 11, September 15, 2005, pages 1135-1146.
6. Food and Drug Administration (FDA). FDA Approves First Oral Drug for Chronic Iron Overload. FDA News, November 9, 2005,
7. Schrier, S. New Treatment Options for Thalassemia. Clinical Advances in Hematology and Oncology, volume 2, number 12, December 2004.
8. American College of Obstetricians and Gynecologists (ACOG). Hemoglobinopathies in Pregnancy. ACOG Practice Bulletin, number 64, July 2005.
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