Thalassemia is an inherited disorder that affects the production of hemoglobin and causes anemia. Hemoglobin is the substance in red blood cells that enables them to transport oxygen throughout the body. It is composed of a heme molecule and protein molecules called globins. Owing to an inherited genetic trait, lower-than-normal amounts of globins are manufactured in the bone marrow. If the trait is inherited from both parents, a globin may be entirely absent. Thalassemia causes varying degrees of anemia, which can range from insignificant to life threatening. The resulting anemia triggers a surge in red blood cell production, but the new cells are also defective. The bone marrow expands as it attempts to keep pace with the perceived need for new red blood cells, setting the stage for bone deformity and pain. Jaundice, indicated by yellowed skin, can result from high levels of bilirubin (the end product of hemoglobin degradation). The spleen can become abnormally large and effects on the immune system increase the vulnerability to infection. At the same time, alot of energy is invested in red blood cell production, stunting developmentand growth.
Humans have the genes to construct six types of globins, but do not use all six at once. Different globins are produced depending on the stage of development: embryonic, fetal, or adult. There is a different gene for each type of globin, with the exception of alpha-globin, which has two genes. (Genes are inherited in pairs, one copy from each parent.) A gene mutation may lead to inadequate levels of the related globin, reduced hemoglobin formation, and anemia. Such mutations are the underlying cause of thalassemia. Thalassemia is classified according to the globin that is affected. The most common types of thalassemia are beta-thalassemia and alpha-thalassemia. Beta-thalassemia is caused by a mutation in the gene responsible for beta-globin. If a mutated beta-globin gene is inherited from both parents, the result is beta-thalassemia major, a severe, potentially life-threatening anemia. Beta-thalassemia major may also be referred to as Cooley's anemia or erythroblastic anemia. If only one mutated copy of the beta-globin gene is inherited, mild-to-nonexistent symptoms may appear; this condition is called beta-thalassemia minor. A person with one mutated copy of the beta-globin gene is referred to as a carrier of the beta-thalassemia trait.
The alpha-thalassemias are more complex because a person inherits two alpha-globin genes from each parent, yielding a total of two pairs of alpha-globin genes. Mutations in these genes can give rise to a range of symptoms. As longas adequate levels of alpha-globins are produced, the person--otherwise, called the carrier of the alpha-thalassemia trait--will have few, if any symptoms. In cases in which alpha-globin is severely reduced, or not produced at all,the consequences can be fatal during fetal development or shortly after birth.
People with Mediterranean (including North African), Middle Eastern, or southeast Asian ancestry are at higher risk of being carriers of or developing beta-thalassemia than are other populations. Alpha-thalassemia also is more likely to affect people of Mediterranean, African, Middle Eastern, and southeastAsian descent. In some areas, 1 in 150-200 children are born with thalassemiamajor. It has been estimated that 2 million people in America carry the thalassemia trait. When two carriers of the same type thalassemia produce a child, there is a 25% possibility that the child will inherit moderate or severe thalassemia.
Thalassemia may be diagnosed from the symptoms; however, with proper medicaltreatment, a diagnosis may be made before symptoms become life- or health-threatening. Basic information that is used in diagnosis includes race and ethnic background, family history, and age. Unexpectedly slow development, along with pallor, jaundice, enlarged spleen or liver, or deformed bones can be common signs of thalassemia.
Laboratory tests are used to confirm a diagnosis and determine the type of thalassemia. These tests can also be used to identify carriers. A blood count is done in which the numbers of red blood cells are calculated. The size of the blood cells and the ratio of mature to immature cells are also determined.A higher-than-normal presence of unusually small or immature red blood cellsindicate a problem in red blood cell production. Further tests measure the amount of hemoglobin; a low concentration indicates anemia. Hemoglobin molecules can be separated based on the component globin molecules, which aids in diagnosing the type of thalassemia. This process is known as hemoglobin electrophoresis.
Thalassemia cannot be cured; therapy focuses on managing symptoms. Treatmentis not necessary for individuals who are unaffected or only develop mild symptoms. The mainstays of thalassemia management are blood transfusions and ironchelation therapy. Blood transfusions are typically given every 6-8 weeks, but may be more frequent in some cases. These transfusions have two purposes:to keep hemoglobin at or near normal levels and to prevent the bone marrow from producing ineffective red blood cells. Repeated transfusions carry the risk of iron loading, a condition in which the body accumulates too much iron. As the iron stores become too large, iron deposits form in the liver, heart, and endocrine glands. These iron deposits cause organ damage and, left unchecked, death. Iron chelation therapy begins between ages three to five with desferrioxamine. The desferrioxamine is administered under the skin of the abdomen or via an implanted venous (vein) port. Once the appropriate dose for an individual is determined, the drug must be administered on a daily or near-daily basis.
Thalassemia has been treated with bone marrow transplantation. However, bonemarrow transplants are strictly limited by several factors, including the general health of the marrow recipient and whether a donor with compatible marrow can be found. Bone marrow transplants are risky--fatality rates range between 10-30%--and success cannot be guaranteed.
Once the genes that determine thalassemia are inherited, the disease cannot be prevented. Screening offers the opportunity of identifying thalassemia carriers. Carriers may decide to undergo genetic testing and counseling to assesspotential risks to their children. Finally, prenatal testing, usually chorionic villus sampling or amniotic fluid testing, allows identification of thalassemia in unborn children.