Thalassemia Causes

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Thalassemia is an inherited blood disorder that causes your body to produce less hemoglobin than normal. Hemoglobin is a protein in red blood cells that helps them carry oxygen to all parts of the body. Hemoglobin is made of two kinds of protein chains called alpha globin and beta globin. Thalassemia develops when faulty genes prevent your body from making the right amount of alpha globin or beta globin chains. When this happens, red blood cells cannot carry enough oxygen to your body’s organs and tissues.

If you inherit faulty hemoglobin genes from one parent but normal genes from the other, you are called a “carrier.” Carriers often have no signs of illness or they may experience mild anemia. However, they can pass the faulty genes on to their children. If you inherit faulty genes from both parents, your disease may be moderate to serious. The two types of thalassemia are alpha thalassemia and beta thalassemia.

How does alpha thalassemia develop?

You need four genes (two from each parent) to make enough alpha globin protein chains. If one or more of the genes is missing, you will have alpha thalassemia, which means your body does not make enough alpha globin protein.

• If you’re only missing one gene, you're a “silent” carrier. This means you won't have any signs of illness.
• If you’re missing two genes, you have alpha thalassemia trait (also called alpha thalassemia minor). This means you may have mild symptoms of anemia.
• If you’re missing three genes, you likely have hemoglobin H disease (which a blood test can detect). This type of thalassemia causes moderate to severe anemia.
• Very rarely, a baby is missing all four genes. This condition is called alpha thalassemia major or hydrops fetalis. Babies who have hydrops fetalis usually die before or shortly after birth.

Example of an inheritance pattern for alpha thalassemia

In the image, the alpha globin genes are located on chromosome 16. A child inherits four alpha globin genes (two from each parent). In this example, the father is missing two alpha globin genes and the mother is missing one alpha globin gene. Each child has a 25% chance of inheriting two missing genes and two normal genes (thalassemia trait), three missing genes and one normal gene (hemoglobin H disease), four normal genes (no anemia), or one missing gene and three normal genes (silent carrier).

How does beta thalassemia develop?

You need two genes (one from each parent) to make enough beta globin protein chains. If one or both of these genes are altered, you’ll have beta thalassemia. This means that your body won’t make enough beta globin protein.

• If you have one altered gene, you’re a carrier. This condition is called beta thalassemia trait or beta thalassemia minor. It causes mild anemia symptoms.
• If both genes are altered, you’ll have beta thalassemia intermedia or beta thalassemia major (also called Cooley's anemia). The intermedia form of the disorder causes moderate anemia. The major form causes serious anemia symptoms.

Example of an inheritance pattern for beta thalassemia

In the image, the beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent). In this example, each parent has one altered beta globin gene. Each child has a 25% chance of inheriting two normal genes (no anemia), a 50% chance of inheriting one altered gene and one normal gene (beta thalassemia trait), or a 25% chance of inheriting two altered genes (beta thalassemia major).

You may be more likely to have thalassemia based on your family history and genetics and your race or ethnicity.

Family history and genetics

If your parents have mutations in the alpha globin or beta globin genes, or in other genes that affect the alpha or beta globin proteins chains, then you can inherit thalassemia. If someone in your family has thalassemia, you may be a carrier. Carriers can pass the condition on to their children.

Race or ethnicity

Thalassemia occurs most often among people of South Asian, Italian, Greek, Middle Eastern, and African descent.

People of South Asian descent are more likely than other groups to have at least two missing alpha globin genes, causing more severe alpha thalassemia (hemoglobin H disease or alpha thalassemia major).

Since thalassemia is caused by changes (mutations) in genes, there is no way to prevent it. People who do not know whether they carry a faulty gene that can cause thalassemia can ask their healthcare provider for a blood test.

Couples who are planning to have children and know that they are at risk of having a child with thalassemia may want to meet with a genetic counselor. A genetic counselor can answer questions about the risk and explain the choices that are available.

If you are pregnant and you or your partner has a family history of thalassemia, your provider may also recommend prenatal testing. Prenatal testing is done using a sample of amniotic fluid, the liquid in the sac surrounding a growing embryo, or of tissue taken from the placenta, the organ that attaches the umbilical cord to the mother’s womb. Testing before birth is safe and can be done as early as 8 to 10 weeks into the pregnancy.