What is thalassemia?
Thalassemias are blood disorders that are inherited from parents who carry genes for thalassemia trait to their children. Thalassemias cause the body to produce fewer healthy red blood cells and less hemoglobin, the iron-rich protein in red blood cells that carries oxygen to all parts of the body. People who have thalassemia have mild to severe anemia. Thalassemias affect males and females. The disorders occur most often among people of Italian, Greek, Middle Eastern, Southern Asian, and African descent. Severe forms usually are diagnosed in early childhood and are lifelong conditions.
A normal hemoglobin has four protein chains, two alpha globin and two beta globin. The two major types of thalassemia, alpha or beta, are named after defects in the specific for alpha or beta globin. The signs and symptoms of thalassemia are related to the number of genes affected or absent, causing different degrees of anemia. People who have alpha or beta thalassemia trait may asymptomatic or have mild anemia. People with more serious forms of thalassemia lack more than one functioning globin gene.
Four alpha globin genes, two from each parent, are needed to make the normal amount of alpha globin protein chains. A “silent carrier” is missing one alpha globin gene and is completely normal. Alpha thalassemia trait occurs if two of the four genes are missing. Hemoglobin H occurs when three alpha genes are absent, Hemoglobin H causing moderate to severe anemia. People who have hemoglobin H disease (absent three functioning alpha globin genes) usually have signs and symptoms within the first 6-10 years of life, and may include the following health problems: delayed growth and development, tiredness, bone problems such as osteoporesis or enlarged spleen and liver.
The most severe form of alpha thalassemia is called alpha thalassemia major or hydrops fetalis. Babies who have this disorder usually die before or shortly after birth.
Two beta globin genes, one from each parent, are needed to make enough beta globin protein chains. If one beta gene is absent or abnormal, the condition is called beta thalassemia trait, and causes a mild anemia. If both beta genes are absent or affected, the result is moderate to severe anemia. The severe form of beta thalassemia is known as thalassemia major, beta-zero (ß0) thalassemia or Cooley’s anemia. People who have beta thalassemia major (lacking both beta globin genes) usually have signs and symptoms within the first two years of life, and may include the following health problems: delayed growth and development, tiredness, bone problems such as osteoporesis, enlarged spleen and liver, risk of heart failure.
We diagnose thalassemia by obtaining a complete blood count. Typical blood count results are a low hemoglobin level and small red blood cells, consistent with microcytic anemia. Diagnosis is usually confirmed by an abnormal hemoglobin electrophoresis, although sometimes genetic testing is needed to confirm the diagnosis.
Because the alpha or beta globin genes for thalassemias are inherited from parents to children, family genetic studies also can help diagnose the disorder. These studies involve taking a family medical history and doing blood tests on family members to test their alpha or beta globin genes. Parents expecting a baby and known to be thalassemia carriers may want to consider prenatal testing, done by analyzing a sample of amniotic fluid or tissue from the placenta.
For people who have moderate or severe alpha or beta thalassemias, transfusions of red blood cells are the main treatment by providing healthy cells with normal hemoglobin. Transfused red blood cells last only about one month, so repeated transfusions as often as every three to four weeks, is necessary to maintain a healthy supply of red blood cells. The hemoglobin in red blood cells is an iron-rich protein. Thus, regular blood transfusions can lead to a condition called “iron overload” that is damaging to the heart, liver, and other organs of the body. To prevent this damage, removal of excess iron from the body is required through iron chelation therapy. Iron chelation usually is effective through a swallowed medication, normally deferasirox. Folic acid supplements are used as well.
A stem cell transplant is the only treatment that can cure thalassemia. The transplant replaced the abnormal stem cells of the patient with normal stem cells from a compatible donor. Researchers are working to find new treatments for thalassemias. For example, it might be possible someday to insert a normal hemoglobin gene into stem cells in bone marrow. This will allow people who have thalassemias to make their own healthy red blood cells and hemoglobin.