Thalassemia

Thalassemia, also called Mediterranean Anemia, is an inherited autosomal recessive blood disease of hemoglobin synthesis. Hemoglobin is the oxygen-carrying part of the red blood cells. It consists of two different proteins, an alpha and a beta. In thalassemia, the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, and this in turn causes mild or severe anemia which is the common symptom of the thalassemias.

The two main types of thalassemia include alpha thalassemia and beta thalassemia:
Individuals with alpha thalassemia do not produce enough alpha globin.
Those with beta thalassemia do not produce enough beta globin.

What is alpha thalassemia?
Alpha thalassemia occurs when one or more of the four alpha chain genes related to the alpha globin protein are missing or changed. Alpha chain protein production is evenly divided among the four genes. With alpha thalassemia, the "failed" genes are almost invariably lost from the cell due to a genetic accident. The severity of the condition is determined by how many of these genes are missing or abnormal.

Silent Carrier, is the loss of one gene diminishes the production of the alpha protein only slightly. The silent carrier will have normal hemoglobin levels and red cell indices but can pass on the affected gene to their offspring. Often, these individuals are identified only after having a child with Hb H disease or alpha thalassemia trait. The only way to diagnose this condition is by DNA analysis.

Alpha thalassemia trait, also called alpha thalassemia minor, is the loss of two genes (two-gene deletion alpha thalassemia) produces a condition with small red blood cells. In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. The condition can be detected by routine blood testing.

Hemoglobin H Disease, is the loss of three alpha genes produces a serious hematological problem. With this condition, the large decrease in the amount of alpha globin chains produced causes an excess of beta chains, which then aggregate into beta tetramers (groups of 4 beta chains), known as Hemoglobin H. Hemoglobin H has two problems. First it does not carry oxygen properly, making it functionally useless to the cell. Second, hemoglobin H protein damages the membrane that surrounds the red cell, accelerating cell destruction. The combination of the very low production of alpha chains and destruction of red cells in hemoglobin H disease produces a severe, life-threatening anemia.

Alpha Thalassemia Major, is the loss of all four alpha genes produces a condition that is incompatible with life. In this condition, there are no alpha genes in the individual's DNA, which causes the gamma globins produced by the fetus to form an abnormal hemoglobin called hemoglobin Barts. Most individuals with this condition die before or shortly after birth. In some extremely rare cases where the condition is discovered before birth, in utero blood transfusions have allowed the birth of children with hydrops fetalis who then require lifelong blood transfusions and medical care.

What is beta thalassemia?
The fact that there are only two genes for the beta chain of hemoglobin makes beta thalassemia a bit simpler to understand than alpha thalassemia. Unlike alpha thalassemia, beta thalassemia rarely arises from the complete loss of a beta globin gene. The beta globin gene is present, but produces little beta globin protein. The degree of suppression varies. Many causes of suppressed beta globin gene expression have been found. The severity of the condition is determined by whether one or both beta globin genes carry a mutation and by the severity of the mutation.

Thalassemia Trait, also called Thalassemia Minor, is caused by a mutation on one beta globin gene. In this condition, the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin. A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia. As in mild alpha thalassemia, physicians often mistake the small red blood cells of the person with beta thalassemia minor as a sign of iron-deficiency anemia and incorrectly prescribe iron supplements.

Thalassemia major, also called Cooley's anemiathe, is two-gene beta thalassemia produces a severe anemia. The severity of the disorder depends in part on the combination of genes that have been inherited: beta-0-thal/ beta-0-thal; beta-0-thal/ beta-(+)-thal; beta-(+)-thal/ beta-(+)-thal. The beta-(+)-thalassemia genes vary greatly in their ability to produce normal hemoglobin. This condition usually appears in an infant after three months of age and causes life-threatening anemia. This anemia requires lifelong regular blood transfusions and considerable ongoing medical care. Left untreated, this excess iron can deposit into the liver, heart and other organs and can lead to a premature death from organ failure.