Hemoglobinopathies

The thalassemias are a group of hemoglobinopathies that, like sickle cell disease, are caused by a genetic change. Unlike sickle cell disease, however, the genetic change does not result in the production of an abnormal form of the globin molecule. Instead, the bone marrow synthesizes insufficient amounts of a hemoglobin chain. This, in turn, reduces the production of red blood cells and causes anemia.

Either the alpha or beta chain may be affected, but beta thalassemias are more common. Individuals who are heterozygous for this disorder have one allele for this disease and one normal allele and are said to have thalassemia minor. They usually produce sufficient beta globin so that they have only mild anemia. They may not have any symptoms at all. Thalassemia minor is sometimes misdiagnosed as iron deficiency anemia.

If two individuals with thalassemia minor have children, there is a onein-four chance that each child will inherit an abnormal gene from both parents and will be homozygous for the disorder.

Individuals who are homozygous for this condition may develop either thalassemia intermedia or thalassemia major. Newborn babies are healthy because their bodies are still producing HbF, which does not have beta chains. During the first few months of life, the bone marrow switches to producing HbA, and symptoms start to appear.

In thalassemia major, also called Cooley's anemia, the bone marrow does not synthesize beta globin at all. Children affected by thalassemia major become very anemic and require frequent blood transfusions. They are so ill that they often die by early adulthood.

In thalassemia intermedia, the production of beta globin is decreased, but not completely. People with this disease have anemia, but they do not require chronic blood transfusions to stay alive.

Alpha thalassemia is more complicated, because an individual inherits two alpha globin genes from each parent for a total of four alpha globin genes. Thus a person can inherit anywhere from zero to four normal genes.

The more abnormal alpha genes that are inherited, the greater the symptoms. If an individual does not have any functional alpha genes, the body cannot produce any alpha globin. Since HbF requires alpha chains, the developing fetus does not produce healthy hemoglobin and shows severe symptoms even before birth. This condition is almost always fatal, with affected infants dying either before or shortly after delivery.

The loss of three functional alpha genes produces severe anemia, the loss of two functional genes typically causes mild anemia, and the loss of only one gene usually does not produce any symptoms. The thalassemias most commonly occur in people from Italy, Greece, the Middle East, Africa, and Southeast Asia; and in their descendants.