Skip to main content

Genetic: Thalassemia

Genetic: Thalassemia

Causes and Symptoms
The Future
For more information


Thalassemia is the name of a group of inherited blood disorders caused by various mutations in the genes that affect the body's ability to produce hemoglobin, the oxygen-carrying pigment in red blood cells. Some doctors prefer to speak of the thalassemias (in the plural) to underscore the fact that they are a group of blood disorders rather than a single disease.


There are two major types of thalassemia, categorized according to the part of the hemoglobin molecule that is affected by the genetic

mutations. The hemoglobin molecule has four protein chains, two called alpha chains and two called beta chains. Thalassemias are classified as alpha thalassemias if the genetic mutation damages the alpha chain, and beta thalassemias if the genetic mutation affects the beta chain.

Four genes are needed to make the proteins in the alpha chains of the hemoglobin molecule. If one or two of these genes are defective, the person has what is called thalassemia trait. They will not have the symptoms of thalassemia but will carry the genetic mutation. A child who inherits two thalassemia trait genes (one from each parent) will have the symptoms of the disease. A child of two carriers has a 25 percent chance of receiving two trait genes and developing the disease and a 50 percent chance of being a thalassemia trait carrier.

On the other hand, if the person has defects in more than two of the four genes needed to make the proteins in the alpha chain, they will have moderate to severe anemia. The most severe form of alpha thalassemia is known as alpha thalassemia major or hydrops fetalis. Babies with hydrops fetalis usually die before or shortly after birth.

In beta thalassemia, the person has mutations in one or both of the genes needed to form the beta chain of the hemoglobin molecule. The severity of beta thalassemia depends on the extent of the changes in one or both genes. If both genes are affected, the result is moderate to severe anemia. The severe form of beta thalassemia is sometimes called thalassemia major or Cooley's anemia.


The demographic distribution of alpha thalassemia is different from that of beta thalassemia. The rate of alpha thalassemia in the United States is rising due to immigration from countries where the mutations that

cause this type of thalassemia are relatively common. These include countries in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the countries around the Mediterranean Sea. About 300,000–400,000 severely affected infants are born worldwide every year; more than 95 percent of these births occur in Asia, India, and the Middle East.

Doctors estimate that about 15 percent of African Americans are silent carriers of alpha thalassemia. In addition, thalassemia trait (minor) occurs in 3 percent of African Americans and in 1–15 percent of persons from Mediterranean countries.

Beta thalassemia is more common in Africa, Southeast Asia, Iran, Arabia, Central Asia, and the countries around the Mediterranean than it is in northern Europe or North America. It may affect as many as 10 percent of the population in Southeast Asia and Africa.

Males and females are equally affected by both alpha and beta thalassemia.

Causes and Symptoms

Both alpha and beta thalassemia are caused by mutations in genes that affect the structure of the hemoglobin molecule. In alpha thalassemia, one or more of four genes (two from each parent) located on chromo-some 16 are defective. In beta thalassemia, the mutation is located in the HBB gene on chromosome 11.

The symptoms of alpha thalassemia range from no symptoms in carriers of the thalassemia trait to mild or severe symptoms of the disease, depending on the number of genes that are defective.

  • Thalassemia trait. This is a mild form of alpha thalassemia in which the person has red blood cells that are smaller than normal and a mild anemia, but no major health problems. It is often mis-diagnosed by doctors as iron deficiency anemia.
  • Hemoglobin H disease. This is a form of alpha thalassemia in which the lack of alpha protein is great enough to cause severe anemia and such serious health problems as an enlarged spleen, deformed bones, leg ulcers, gallstones, and fatigue. It is named for the abnormal type of hemoglobin that is formed by the beta proteins in the hemoglobin molecule. Children with hemoglobin H disease are often born with jaundice and anemia; the condition is usually detected shortly after birth.
  • Alpha thalassemia major or hydrops fetalis. In this condition there are no functional alpha proteins at all in the patient's hemoglobin. Babies with hydrops fetalis die before or shortly after birth.

Beta thalassemia is classified into three types, thalassemia minor, thalassemia intermedia, and thalassemia major (Cooley's anemia) depending on the severity of symptoms.

  • Thalassemia minor: Persons with this form of beta thalassemia usually experience no health problems except for an occasional mild anemia. Their condition is usually discovered only through a routine blood test.
  • Thalassemia intermedia: Children with this form of beta thalassemia may require occasional blood transfusions to treat their anemia. Bone deformities and enlargement of the spleen are common.
  • Thalassemia major: This is a potentially life-threatening form of beta thalassemia. Children with Cooley's anemia must receive regular blood transfusions and extensive medical care in order to survive past childhood.


Both major types of thalassemia are diagnosed by blood tests and genetic testing. Genetic testing can determine whether a person is a carrier of thalassemia even though they may not have symptoms.

Genetic testing can be done before a baby is born, around the eleventh week of pregnancy. The doctor can remove a small amount of tissue from the placenta for analysis. Amniocentesis, which involves taking a sample of the fluid surrounding the baby in the uterus, can be performed around the sixteenth week of pregnancy.


Treatment depends on the severity of thalassemia. People with trait thalassemia may not have symptoms that need treatment. Patients with hemoglobin H disease and Cooley's anemia typically require frequent blood transfusions for the rest of their lives along with a type of therapy called chelation therapy. Most patients with a major form of thalassemia are given red blood cell transfusions every two to three weeks, as much as fifty-two pints of blood per year. These transfusions are necessary to

make sure that the patient's blood is delivering enough oxygen to the tissues to meet energy needs.

Chelation therapy consists of a medication administered to help the body get rid of the iron that builds up in tissues as a result of frequent blood transfusions. If the excess iron is not removed, it will eventually damage the patient's liver and heart and lead to early death from organ failure. Chelation therapy for severe thalassemia involves the use of Desferal, a drug that is infused into the body through a pump worn under the skin of the stomach or legs five to seven times a week for as long as twelve hours. A newer drug for chelation therapy was approved by the Food and Drug Administration (FDA) in 2005. It can be taken by mouth just once a day. Both drugs work by changing the iron into a form that the body can excrete through the urine or stool.

Patients with beta thalassemia major (Cooley's anemia) usually have the spleen removed by surgery after they are six or seven years of age to prevent later complications and lower the frequency of blood transfusions required. Another treatment that is effective if a good donor match can be found is transplantation of bone marrow. Transplantation, however, is possible only for a small minority of patients who have a suitable bone marrow donor. The transplant procedure itself is still risky and can result in the patient's death.


The prognosis of thalassemia depends on the type and the severity. Carriers of alpha thalassemia who do not have symptoms have a normal life expectancy and usually enjoy good health, although they should consider genetic counseling before starting a family. Patients with hemoglobin H generally survive into adulthood, although some have a lowered quality of life because of the disease. Hydrops fetalis is almost always fatal.

Patients with mild beta thalassemia have a normal life expectancy with generally good health, although like patients with alpha thalassemia, they should be informed about the hereditary nature of their condition. The prognosis for patients with Cooley's anemia depends on their compliance with frequent transfusions and chelation therapy. Some people find Desferal therapy so troublesome and painful that they give up on treatment. Untreated, Cooley's anemia usually leads to death from heart failure or infection before age twenty.


There is no way to prevent either alpha or beta thalassemia.

The Future

Researchers are hoping to develop a form of gene therapy to treat patients with beta thalassemia. This type of treatment would involve inserting normal HBB genes into immature bone marrow cells. These are the cells that produce red blood cells; thus gene substitution would lead to the eventual production of normal red blood cells.

SEE ALSO Anemias


Anemia: A condition in which there are not enough red cells in the blood or enough hemoglobin in the red blood cells.

Chelation therapy: A form of treatment to reduce overly high levels of iron (or other metals) in the body by giving the patient a chemical that allows the body to get rid of the excess metal in urine or stool.

Cooley's anemia: Another name for the most severe form of beta-thalassemia.

Hemoglobin: A pigment in red blood cells that contains iron and transports oxygen from the lungs to other body tissues.

Hydrops fetalis: The most severe form of alpha thalassemia, leading to death before or shortly after birth.

Thalassemia trait: A condition in which a person is missing one or two genes required to make the proteins in the alpha chains of the hemoglobin molecule. The person does not have the symptoms of thalassemia but can pass the genetic deficiency to their children.

For more information


Thalassemia. San Diego, CA: ICON Health Publications, 2004.


Cooley's Anemia Foundation. What Is Thalassemia? Available online at (accessed May 30, 2008).

Genetics Home Reference. Beta Thalassemia. Available online at (accessed May 30, 2008).

National Center for Biotechnology Information (NCBI). Genes and Disease: Thalassemia. Available online at (accessed May 30, 2008).

National Heart, Lung, and Blood Institute (NHLBI). What Are Thalassemias? Available online at (accessed January 2008; cited May 29, 2008).

National Human Genome Research Institute (NHGRI). Learning about Thalassemia. Available online at (accessed November 25, 2007; cited May 29, 2008).

Nemours Foundation. Thalassemias. Available online at (accessed May 30, 2008).

Cite this article
Pick a style below, and copy the text for your bibliography.

  • MLA
  • Chicago
  • APA

"Genetic: Thalassemia." UXL Encyclopedia of Diseases and Disorders. . 23 Jan. 2019 <>.

"Genetic: Thalassemia." UXL Encyclopedia of Diseases and Disorders. . (January 23, 2019).

"Genetic: Thalassemia." UXL Encyclopedia of Diseases and Disorders. . Retrieved January 23, 2019 from

Learn more about citation styles

Citation styles gives you the ability to cite reference entries and articles according to common styles from the Modern Language Association (MLA), The Chicago Manual of Style, and the American Psychological Association (APA).

Within the “Cite this article” tool, pick a style to see how all available information looks when formatted according to that style. Then, copy and paste the text into your bibliography or works cited list.

Because each style has its own formatting nuances that evolve over time and not all information is available for every reference entry or article, cannot guarantee each citation it generates. Therefore, it’s best to use citations as a starting point before checking the style against your school or publication’s requirements and the most-recent information available at these sites:

Modern Language Association

The Chicago Manual of Style

American Psychological Association

  • Most online reference entries and articles do not have page numbers. Therefore, that information is unavailable for most content. However, the date of retrieval is often important. Refer to each style’s convention regarding the best way to format page numbers and retrieval dates.
  • In addition to the MLA, Chicago, and APA styles, your school, university, publication, or institution may have its own requirements for citations. Therefore, be sure to refer to those guidelines when editing your bibliography or works cited list.