Elizabeth McPherson, M.D., associate professor of human genetics at the University of Pittsburgh, explains:

Image: BRYN MAWR COLLEGE HEMOGLOBIN. A normal molecule has two a globin chains and two b globin chains, each having a heme group with an iron center.

Thalassemia is a genetic disorder in which there is decreased production of one of the globin chains found in hemoglobin. This oxygen-transporting molecule in blood normally contains four globin chains, two alpha (a) and two non-a, each with its own heme group (made of an iron atom bound in protoporphyrin ring). In adults, more than 90 percent have type A1 hemoglobin, containing two a and two beta (b) globin chains. A small amount carry a variant called hemoglobin A2, having two a and two delta (d) chains. Infants are born with a slightly different type called fetal hemoglobin, with two a chains and two gamma (g) chains. If the body fails to produce enough of any one type of globin, a deficiency of hemoglobin can result, causing anemia.

Sometimes the body manufactures abnormal hemoglobin, containing yet another combination of chains. Such abnormal hemoglobins often do not transport oxygen efficiently and may also be unstable. The presence of unstable hemoglobins is extremely harmful; the bone marrow must overwork to make more hemoglobin and the liver and spleen become stressed by the need to remove wastes from the breakdown of the unstable hemoglobin. In the case of sickle cell disease, the problem is the characteristic behavior of abnormal sickle hemoglobin. But thalassemia is different: Instead of abnormal hemoglobin, the main problem is a decreased amount of normal globin.

Thalassemias differ in severity and in the type of globin chain that is deficient. The most common type in the United States is b thalassemia, also known as Mediterranean anemia in its mild form or Cooley's anemia in its severe form. A pair of genes controls the production of the b globin chain.

If a person has total absence or severe defects in both b globin genes, he or she will have no b globin and so no hemoglobin A1. Other hemoglobins such as A2 and fetal hemoglobin that do not contain b chains will be made. After the first few months of life, however, the quantity of these other hemoglobins diminishes.

A person with b thalassemia major, in which both genes are affected, develops severe anemia starting at a few months of age. Because the bone marrow must struggle to make enough hemoglobin, the marrow cavities enlarge, causing deformities especially in the facial bones. In addition, because the spleen is constantly working to remove abnormal blood cells from the circulation, it too enlarges. Patients with b thalassemia major can survive only with the help of frequent blood transfusions. Another danger for people with b thalassemia is an iron overload from the gradual breakdown of the transfused blood. A treatment called chelation is then needed to remove excess iron.

People who have an absence or severe abnormality of only one of their b globin genes have b thalassemia minor. This non-life threatening form of the disease causes only mild anemia and does not generally require treatment. Even so, it is important to diagnose b thalassemia minor (also called thalassemia trait) because iron treatment for affected individuals does not help their anemia and may even be harmful. Also if two people with b thalassemia minor have a child, the child may inherit a defective b globin gene from both parents and be born with b thalassemia major.

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