Prevention & Risk Assessment
What causes alpha thalassemia?
Alpha thalassemia is caused by mutations in the alpha chain of the hemoglobin molecule. Normally, there are two alpha chain genes located on each #16 chromosome, for a total of 4. The alpha chain is an important component of fetal hemoglobin (which is usually made before birth) and hemoglobin A and hemoglobin A2 (which are present after birth). How these genes are altered determines the specific type of alpha thalassemia in a child:
- Alpha thalassemia major (also called Hb Bart syndrome). With this disorder, all four alpha chain genes are deleted. Alpha thalassemia major develops before birth and results in hydrops fetalis, a condition in which the body has excess fluid. The fetus can also have other problems including severe anemia, enlargement of the liver and spleen (hepatosplenomegaly), and defects in the heart, urinary system, or genitals. Most babies with hydrops fetalis due to alpha thalassemia major die during pregnancy or soon after birth. The mother can have pregnancy complications including preeclampsia (high blood pressure), bleeding problems, and preterm delivery.
- Hemoglobin H disease. Three alpha chain genes are deleted. Hemoglobin H disease occurs when a person has only one functioning alpha chain gene, resulting in a hemolytic anemia that can worsen with febrile illness or exposure to certain drugs, chemicals, or infectious agents. People with hemoglobin H disease are at increased risk to have a child with alpha thalassemia major, since they carry one #16 chromosome with an alpha chain two gene deletion (cis deletion).
- Alpha thalassemia carrier. Two alpha chain genes are deleted, either:
- Both from the same #16 chromosome, called a cis deletion
- One from each #16 chromosomes, called a trans deletion
- Silent alpha thalassemia carrier. One alpha chain gene is deleted (the other three are normal). Blood tests are usually normal, and the only way to confirm a silent carrier is by DNA studies.
When both parents are carriers of the cis deletion, there is a one in four, or 25 percent, chance with each pregnancy, to have a baby with alpha thalassemia major. A common hemoglobin test, hemoglobin electrophoresis, cannot diagnose alpha thalassemia. Carriers of the cis deletion versus the trans deletion can be distinguished by DNA analysis only. DNA testing is usually done from a blood sample to look at the alpha chain genes on each #16 chromosome to determine which genes are deleted.