There are two major types of thalassemias, and each affects a different part of a hemoglobin molecule. Two different protein chains – alpha chains and beta chains – make up a hemoglobin molecule. An abnormality on either of these chains affects how red blood cells form, and their eventual size and shape. The two types of thalassemias are called alpha thalassemia and beta thalassemia, depending on which protein is affected.

Alpha thalassemia occurs in people with abnormalities in at least one of the four genes that produce alpha protein chains. The forms from mildest to most severe include:

• Silent carrier state. One gene is affected, and the lack of alpha protein is so small that patients rarely have any symptoms. A mutation of the alpha globin can lead to a version of this disease known as hemoglobin constant spring, which also causes few if any symptoms.
  
  
• Alpha thalassemia trait. Also known as mild alpha thalassemia, two genes are affected and even less alpha protein is present than in silent carrier state. Patients have smaller red blood cells and may have mild anemia. Some patients do not experience any symptoms. This condition is often mistaken for iron deficiency anemia, as the symptoms are similar. Taking iron supplements will not effectively treat this form of anemia.
  
  
• Hemoglobin H disease. Three genes are affected. The lack of alpha protein is significant enough to cause severe anemia and significant health problems, including enlarged spleen and bone deformities. It is named hemoglobin H after the form of hemoglobin that is produced by the remaining beta protein. A more severe form of this disease known as hemoglobin H-constant spring (resulting from one parent with alpha thalassemia trait and one parent with constant spring) causes even more severe anemia and is more likely to cause spleen enlargement and viral infections. A less severe form of hemoglobin H-constant spring (resulting from two parents who each have constant spring) causes symptoms similar to those of hemoglobin H disease.
  
  
• Alpha thalassemia major. The most severe form of alpha thalassemia, it occurs when all four genes are affected, meaning there are no alpha genes in a person’s DNA. Fetuses with this form of the disease are at high risk of miscarriage, and those who make it through the birthing process usually die shortly thereafter. In rare cases, this condition is discovered before birth, and in utero blood transfusions are begun. After these children are born, they require blood transfusions throughout their lives.

Beta thalassemia is the more common of the two forms of thalassemia in the United States. It occurs when at least one of the two genes involved in making beta protein are affected. The forms of this disease include:

• Beta thalassemia minor. Also known as beta thalassemia trait, it involves one affected gene. Patients have smaller red blood cells and may have mild anemia. Some patients do not experience any symptoms. As with alpha thalassemia trait, this condition is often mistaken for iron deficiency anemia, as the symptoms are similar. Again, iron supplements do not benefits patients with this form of anemia.
  
  
• Beta thalassemia intermedia. Both genes are affected. Patients with this form of the disease have a lack of beta protein in hemoglobin that varies. In some cases, mild anemia may be the only symptom that appears. In others, moderately severe anemia may be accompanied by significant health problems, such as bone deformities and enlargement of the spleen. Unlike beta thalassemia major, patients may require blood transfusions to improve their quality of life rather than to save it.
  
  
• Beta thalassemia major. Also known as Cooley’s anemia, it is a severe form of the disease. Patients have no beta protein in their hemoglobin and require regular blood transfusions if they are to survive. However, these transfusions can cause an overload of iron in the body, which can affect heart and liver function and delay growth and sexual maturation. 

There are also two other forms of thalassemias that result when the gene for either alpha or beta thalassemia pairs with an abnormal or mutant gene:

• E beta thalassemia. Involves hemoglobin E, an abnormal hemoglobin found in people of Southeast Asian ancestry. When combined with beta thalassemia, hemoglobin E produces this condition, which involves moderately severe anemia that produces symptoms similar to beta thalassemia intermedia.
  
  
• Sickle beta thalassemia. Condition produced by combination of beta thalassemia and hemoglobin S, the same form of hemoglobin that is present in sickle cell anemia. The amount of normal beta globin produced by the beta gene determines the severity of this condition. When no beta globin is produced, the condition is very similar to sickle cell anemia. Greater amounts of beta globin result in less severe disease.