Thalassemias are a group of inherited disorders resulting from an imbalance in the production of one of the four chains of amino acids that make up hemoglobin (the oxygen-carrying protein found in red blood cells).

• Symptoms depend on the type of thalassemia.
• Some people have jaundice, skin ulcers, and abdominal fullness or discomfort.
• Diagnosis usually requires special hemoglobin tests.
• Mild thalassemia may not require treatment, but severe thalassemia may require bone marrow transplantation.

Hemoglobin is made up of two pairs of globin chains. Normally, adults have one pair of alpha chains and one pair of beta chains. Sometimes one or more of these chains is abnormal. Thalassemias are categorized according to the amino acid chain affected. The two main types are alpha-thalassemia (the alpha globin chain is affected) and beta-thalassemia (the beta globin chain is affected). Alpha-thalassemia is most common in blacks (25% carry at least one copy of the defective gene), and beta-thalassemia is most common in people from the Mediterranean area and Southeast Asia. Thalassemias are also categorized according to whether people have one copy of the defective gene (thalassemia minor) or two copies of the defective gene (thalassemia major).

All thalassemias have similar symptoms, but they vary in severity. In alpha-thalassemia minor and beta-thalassemia minor, people have mild anemia with no symptoms. In alpha-thalassemia major, people have moderate or severe symptoms of anemia, including fatigue, shortness of breath, paleness, and an enlarged spleen.

In beta-thalassemia major, people have severe symptoms of anemia, and they may also have jaundice, skin ulcers, and gallstones. People may also have an enlarged spleen, which leads to a feeling of fullness and abdominal discomfort. Overactive bone marrow may cause some bones, especially those in the head and face, to thicken and enlarge. The long bones in the arms and legs may weaken and fracture easily.

Children who have beta-thalassemia major may grow more slowly and reach puberty later than they normally would. Because iron absorption may be increased and frequent blood transfusions (providing even more iron) are needed, excessive iron may accumulate and be deposited in the heart muscle, eventually causing iron overload disease and heart failure and early death.

Thalassemias are more difficult to diagnose than other hemoglobin disorders. Testing a drop of blood by electrophoresis is helpful but may be inconclusive, especially for alpha-thalassemia. Therefore, the diagnosis is usually based on special hemoglobin tests and determination of hereditary patterns.

Most people who have a mild thalassemia do not need treatment, but people who have a severe form may need bone marrow transplantation. Gene therapy, in which normal genes are inserted in the person, is being studied but to date has been unsuccessful.

Last full review/revision June 2008 by Alan E. Lichtin, MD