Thalassemia (British spelling "thalassaemia") is caused by a mutated or missing gene that is part of hemoglobin production. Hemoglobin is a protein in red blood cells that is responsible for carrying oxygen. Thalassemia is a hemoglobinopathy, which is a disease of globin protein structures. In thalassemia, the levels of hemoglobin are reduced and there are fewer red blood cells circulating in the blood than normal. A reduced number of red blood cells is also known as anemia, which may be mild or severe.
The structure of the most common form of hemoglobin comprises four protein chains: two alpha hemoglobin (or alpha-globin) proteins and two beta hemoglobin (beta-globin) proteins. Alpha thalassemia occurs when there is a defect in one of the two genes that make alpha hemoglobin and it is classified according to the number of defective genes and the severity of anemia. Beta thalassemia occurs as a result of defective beta hemoglobin proteins and is also classified by the number of defective beta genes and the severity of anemia. The most severe form of beta thalassemia is sometimes called Cooley's anemia.
There is a third form of thalassemia, delta thalassemia, which is not as clinically important as the alpha and beta forms. Only about 3% of hemoglobin contains any delta chains. Therefore, a defect in a delta gene has a limited effect on hemoglobin. Often an individual with delta defects has normal blood cell counts. Even though there is no immediate physical consequence of delta thalassemia, it can interfere with the diagnosis of beta thalassemia, which can be severe.
Thalassemia is an inherited disease that may be inherited as an autosomal recessive or dominant trait depending on the type. Most thalassemias are inherited as recessive traits. Thalassemia is autosomal dominant in a very small percentage of beta thalassemia cases. A person who has only one mutated or defective gene typically does not experience symptoms and is called a carrier (thalassemia trait or thalassemia minor).
It is estimated that 60 to 80 million people worldwide carry the beta thalassemia trait and an estimated 1,000 cases of thalassemia exist in the United States. People with thalassemia are less likely to become infected with malaria, a common infectious disease caused by parasites of the genus Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae). This is because the red blood cells affected by thalassemia are somewhat resistant to infection from the malaria parasite. Thalassemia carriers retain some of this resistance to malaria because some of their red blood cells are abnormal. Therefore, thalassemia occurs more frequently in areas where malaria is also common, including sub-Saharan Africa and other tropical or sub-tropical regions.
Beta thalassemia is considered to be a fairly common blood disorder that is thought to affect several thousand infants every year. Beta thalassemia is more common among people of Mediterranean origin (Greek, Italian, Middle Eastern) and people of Asian and African descent. Alpha thalassemias mostly affect people of Southeast Asian, Indian, Chinese, or Filipino origin.
Signs and symptoms may vary depending on the type and severity of thalassemia. Typically, symptoms that appear are a result of a decrease in circulating oxygen from low hemoglobin and anemia. Some common symptoms include fatigue, shortness of breath, jaundice, and bone deformities in the face. Laboratory tests may also reveal anemia and an enlarged spleen.
Severe thalassemia is treated with blood transfusions and an iron chelator to prevent iron toxicity. Thalassemia can only be cured with a successful bone marrow transplant, but a donor match is necessary and there are risks associated with the procedure. Although thalassemia can be severe and difficult to cure, there are treatment options available. With the proper treatment, patients diagnosed with thalassemia often live normal or near-normal lives.
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types of the disease
Thalassemias are classified as alpha, beta, and rarely delta, depending on which hemoglobin gene is defective. These defects lead to reduced production of the proteins that make up hemoglobin.
Thalassemias can occur together with other hemoglobin defects. Some of the common combinations are with hemoglobin C, E, and S (HbC, HbE, and HbS), in which defective forms of beta hemoglobin cause a related disorder called sickle cell disease (SCD). These combinations result in a mix of different types of anemia (hemolytic and sickle cell) and possible splenomegaly (enlargement of the spleen).
Beta thalassemia: A mutation in the HBB gene, which is responsible for making beta hemoglobin, causes beta thalassemia. The classification of beta thalassemia depends on the level of reduction in beta production. A reduction in beta hemoglobin may result in anemia, depending on the level of functional hemoglobin.
People with beta thalassemia minor or beta thalassemia trait only carry one gene defect and are often asymptomatic or have mild anemia. Mild forms of thalassemia are commonly called beta-plus thalassemia, while severe forms are often referred to as beta-zero-thalassemia. There is a complete absence of beta protein production in beta-zero thalassemia, while beta-plus thalassemia is marked by a deficiency in beta protein production. When two thalassemia gene defects are inherited and moderate anemia is present, the disease is called beta thalassemia intermedia.
Beta thalassemia with severe anemia, in which two thalassemia gene mutations are inherited, is called beta thalassemia major. Severe beta thalassemia is also called Cooley's anemia. Beta defects typically follow an autosomal recessive pattern of inheritance although in a small percentage of cases, the HBB mutation is inherited as an autosomal dominant trait.
Treatment consists of blood transfusions and treatment of transfusion-caused iron overload especially for beta thalassemia major or Cooley's anemia. Beta-thalassemia may only be cured with successful bone marrow transplantation. However, there are risks associated with bone marrow transplants like infection and rejection of the transplant. These risks can be life-threatening and should always be monitored by a healthcare professional.
Alpha thalassemia: There are two genes responsible for the production of alpha hemoglobin: HBA1 and HBA2. Two of each of these genes are inherited from each parent, so each individual has a total of four genes that make alpha hemoglobin.
Alpha thalassemia is classified based on how many of the four genes are defective and the severity of symptoms. When only one gene is defective, the person is called a silent carrier and may have mild or no symptoms of the disease. People with the alpha thalassemia trait or alpha thalassemia minor are carriers with two defective genes and mild anemia. Inheriting three genes results in hemoglobin H disease and is usually associated with severe anemia. If all four genes are defective, then this disorder is called alpha thalassemia major or hydrops fetalis. This is a very rare and serious disease that typically results in death shortly after birth. Alpha thalassemia is inherited as an autosomal recessive trait.
Delta thalassemia: Only about 3% of hemoglobin contains any delta chains, and defects in the delta genes are not very severe. Often an individual with delta defects has normal blood cell counts. Even though there is no immediate physical consequence of delta thalassemia, it can interfere with the diagnosis of beta thalassemias, which can be severe.