What is thalassemia?
Mutations in one or more of the four genes coding for β globin or one or both of the two genes coding for α globin are the causes of thalassemia. The deletions lead to an underproduction of normal hemoglobin, a tetramer of two β and two α globins.
The most severe form of thalassemia is β thalassemia (hydrops fetalis or β thalassemia major), in which all four β globin genes are mutant or deleted and no β globin is produced. Death occurs at or before birth. Milder forms (β thalassemia minor or trait) occur when only two of the β globin genes are nonfunctional or deleted. The mild forms may exhibit mild anemia, but usually no health effects occur. When three β globin genes are deleted or are nonfunctional, the resulting thalassemia is called hemoglobin H disease. Enough β globin is missing in hemoglobin H disease to cause moderate to severe anemia, an enlarged spleen, bone deformities, and fatigue.
In the most severe form of α thalassemia (α thalassemia major or Cooley’s anemia), both α globin genes are nonfunctional or deleted and no normal hemoglobin is produced, resulting in severe anemia. Hemoglobin molecules consisting of four β globin chains rather than two β and two α chains are produced, leading to red blood cell aggregates and inclusions that cause red blood cell membrane damage. In milder forms (α thalassemia minor or trait), in which only one α globin gene is nonfunctional or deleted, hemoglobin production is 50 percent of normal, resulting in mild anemia.
There is no effective treatment for β thalassemia major. Treatment for α thalassemia major involves red blood cell transfusion every two to three weeks. Transfusion therapy results in an iron overload that is controlled using chelators such as Desferal (desferrioxamine).
The thalassemias constitute the most common single-gene inherited disease in the world. People with mild forms of the disease (thalassemia minor or trait) are usually heterozygotes or carriers. When two carriers have children, there is a one in four chance that the child will have the severe form of the disease (thalassemia major). The frequency of the several forms of thalassemia varies geographically, with β thalassemia most common in Africa, the Middle East, India, Southeast Asia, southern China, and around the Mediterranean, and α thalassemia most common in Italy, Greece, the Arabian Peninsula, Iran, Africa, Southeast Asia, and southern China. It has been estimated that two million people in the United States carry one of the genes for thalassemia. The National Institutes of Health recommends testing for the trait.
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