Thalassemias are blood disorders that result in mild to severe anemia, a condition in which too few red blood cells prevent oxygen from being properly circulated in the body. Thalassemias are caused by an inherited disorder that affects how red blood cells are formed and their oxygen-carrying capacity. Specifically, thalassemia affects the development of hemoglobin, which is the protein in blood that carries oxygen. Patients with severe forms of the disorder require regular transfusions of blood.

Hemoglobin is made up of two proteins, known as alpha and beta. Thalassemias can affect either of these proteins, thus the two categories of thalassemia are:

• Alpha thalassemia. Occurs when at least one of the four genes that produce the alpha globin (a type of protein) chain of hemoglobin is either missing or abnormal. If more than two genes are missing, mild to severe anemia will result.
  
  
• Beta thalassemia. Occurs when one or both of the two genes that produce the beta globin chain of hemoglobin are abnormal. The type of abnormality and whether or not one or both genes are affected determine the severity of the disease. When both genes are affected, moderate to severe anemia may result.

The severity of thalassemias depends on how the genes are inherited by a child. If both parents pass on abnormal genes, the child may have a moderate or severe form of thalassemia. Children who inherit an abnormal gene from one parent and a normal gene from another may be carriers of the disease, a condition known as thalassemia trait. This means they will not have the disease themselves, but can pass it on to their children.

People with mild to severe forms of thalassemia may experience anemia that causes symptoms such as fatigue, shortness of breath or heart palpitations. Anemia also causes bone marrow to work harder to create more red blood cells, which can lead to enlargement of bones such as the cheekbones and those of the forehead.

Prenatal testing can help determine if a fetus has thalassemia and how severe the condition is likely to be. A blood test called hemoglobin electrophoresis is performed on newborn infants to check for thalassemia or thalassemia trait. A complete blood count (CBC) also can provide valuable insights into whether or not a patient has thalassemia.

Thalassemia that causes mild anemia may not require specific treatments, though patients with moderate to severe thalassemia may require ongoing therapy. Blood transfusions are the most common form of treatment for severe cases of thalassemia. These transfusions provide the body with healthy red blood cells that carry adequate levels of oxygen. Repeated transfusions can cause excessive levels of iron to build up in the body, a potentially fatal condition known as iron overload (hemochromatosis). A treatment known as chelation therapy can be used to remove excess iron deposits from the body.

Scientists continue to work on new ways to treat thalassemias. For example, one day gene therapy may make it possible to cure thalassemia in fetuses by inserting normal cells into a child’s stem cells.

Couples who are considering having children may want to undergo genetic testing to find out if they are carriers of thalassemias or other disorders that can be passed on to children.

Patients with severe thalassemia are vulnerable to infections that can worsen anemia. As a result, they are urged to receive vaccinations for pneumonia as well as annual flu shots.

Thalassemias are inherited blood diseases that cause defective or reduced production of hemoglobin, the molecule found inside red blood cells that carries oxygen throughout the body. Reduced levels of hemoglobin keep the body from producing adequate levels of healthy red blood cells, a condition known as anemia. Thalassemias are a common form of genetic disorder.

Patients with anemia have less oxygen delivered to the tissues, resulting in a lack of energy. Other symptoms include fatigue, jaundice (yellowing of skin and eyes), shortness of breath, and delayed growth and development in children. Heart failure may develop due to severe anemia. The severity of a thalassemia can vary significantly from patient to patient. Some patients may experience few symptoms, but others may require hospitalization or ongoing treatments.

In recent years, experts have made significant progress in treating thalassemias. As a result, patients with thalassemias now tend to have longer and fuller lives than was previously the case. Patients with severe disease who are diagnosed and treated early may live into their 30s, 40s or beyond. People with less severe forms of the disease, or who are genetic carriers, have a normal life expectancy.

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.

People who have thalassemia inherit the condition from both of their parents. If only one parent has a thalassemia gene, it can still be passed on to a child. However, the child will not have the disease, and instead will become a carrier – meaning the child can pass the gene on to his or her own children later in life. This condition is known as thalassemia trait and does not require medical treatment.

The odds that a couple will pass thalassemia trait or thalassemia disease on to their child in each pregnancy are as follows:

• Parents share same type of thalassemia gene (alpha or beta): 25 percent chance for that type of thalassemia in child
  
  
• Both parents carry genetic trait for beta thalassemia: 25 percent chance of thalessemia major in child
  
  
• One parent has gene for beta thalassemia, other has trait for hemoglobin E: 25 percent chance of E beta thalassemia in child
  
  
• One parent has gene for beta thalassemia, other has trait for hemoglobin S: 25 percent chance of beta sickle thalassemia in child
  
  
• Both parents carry gene for alpha thalassemia AND only one parent has the “cis” type of alpha trait (two alpha globin mutations on same chromosome): 25 percent chance of hemoglobin H disease in child
  
  
• Both parents carry gene for alpha thalassemia AND both parents have the “cis” type of alpha trait (two alpha globin mutations on same chromosome): 25 percent chance of alpha thalassemia major in child
  
  
• One parent carries thalassemia trait and other patient has normal hemoglobin: 50 percent chance child will inherit thalassemia trait, 0 percent chance of inheriting blood disease

Thalassemias are more common among certain ethnic groups, including those of southern European, Mediterranean (e.g., from Turkey, Greece, Italy), African, Chinese and Southeast Asian descent. In recent years, thalassemias have become more common in the United States, largely due to increasing numbers of immigrants from Southeast Asia.

People with mild to severe forms of thalassemia may experience anemia that causes symptoms such as fatigue, shortness of breath or heart palpitations. Severe anemia can affect the growth of children and delay their sexual development. In addition, patients may experience a yellowing of the skin known as jaundice, which results from the destruction of red blood cells. The liver and spleen may become enlarged.

Anemia also causes bone marrow to work harder to create more red blood cells in the body. This bone marrow hyperactivity can lead to enlargement of bones such as the cheekbones and those of the forehead. Abnormalities in the ability of the liver and gallbladder to produce bile can lead to gallstones. Patients also may have protruding abdomens and dark urine.

People who have thalassemia trait rather than thalassemia itself may experience mild anemia, which in turn can cause mild fatigue.

In diagnosing thalassemias, a physician will perform a physical examination and compile a medical history. A family history of thalassemia can be a strong indicator that the patient may have this condition. Genetic testing of family members also can help indicate if a family history of thalassemia is present.  

Prenatal testing can help determine if a fetus has thalassemia, and how severe the condition is likely to be. A blood test called hemoglobin electrophoresis can be performed on newborn infants to check for thalassemia or thalassemia trait. This test, in part, looks for certain types of abnormal hemoglobin in the blood, specifically hemoglobin D or hemoglobin H.

A physician will rule out other conditions before diagnosing alpha thalassemia. For example, the fatigue associated with alpha thalassemia is similar to that caused by an iron deficiency. Blood tests can reveal the amount of iron in a person’s blood, which can help a physician distinguish between a diagnosis of iron deficiency and alpha thalassemia.

A complete blood count (CBC) also can provide valuable insights into whether or not a patient has thalassemia. Normal amounts of hemoglobin in adults range from 12 grams to 18 grams per deciliter of blood. CBC results that detect less hemoglobin than normal, fewer red blood cells than normal and smaller red blood cells than normal may indicate thalassemia.

People who have thalassemia trait generally do not require treatment. Those with mild thalassemia also generally do not require treatment.

Patients with moderate to severe thalassemia may require ongoing therapy. Blood transfusions are the most common form of treatment for severe cases of thalassemia. These transfusions provide the body with healthy red blood cells that carry adequate levels of oxygen. However, blood transfusions provide only temporary therapy and must be repeated for long-term treatment.

Patients with moderate thalassemia may require only occasional transfusions, whereas patients with more severe forms of thalassemia may require regular transfusions. Most patients with significant thalassemia need transfusions that provide an average of 52 pints of blood a year. Transfusions typically are scheduled for every two to three weeks. Patients are also often directed to take folic acid supplements.

Repeated transfusions can cause excessive levels of iron to build up in the body, a potentially fatal condition known as iron overload. Excess iron must be removed to prevent toxic damage to the liver and heart, and abnormal growth rates and delayed sexual development in children.

A treatment known as chelation therapy removes excess iron deposits from the body. It involves injections from a battery-powered infusion pump of an iron-binding drug called desferrioxamine under the skin of the stomach or legs for up to 12 hours a day for five to seven days each week. This drug has been shown to promote normal growth and sexual development and to increase a patient’s lifespan. However, it also can have side effects such as vision damage and hearing loss, and the therapies are often considered inconvenient and painful. Because of this discomfort associated with chelation therapy, many patients discontinue or avoid it. However, this is associated with worsening health problems and early death. Patients are strongly encouraged to continue with their chelation therapy, and physicians are looking for less stressful chelation agents.

Patients who undergo regular transfusions should avoid vitamins or supplements that contain iron because of the dangers of excessive iron levels.

Bone marrow transplants recently have been used to treat especially severe cases of beta thalassemia major. Results have been encouraging, and many patients (typically age 16 or younger) have become disease free. However, bone marrow transplants involve considerable risk, because all the patient’s blood-forming cells must be destroyed and replaced with cells from a donor that perfectly match the patient’s own cells. Typically, these donors are siblings.

Organ damage associated with severe thalassemia may necessitate surgery to remove the affected organ. For example, enlarged spleens may need to be removed, or gallbladders may be removed in patients who have repeated attacks of gallstones.

The blood transfusions associated with thalassemia theoretically put the patient at risk for contracting viruses such as hepatitis or AIDS from contaminated donated blood. However, improved donor screening and testing of blood products have dramatically reduced the risk of such viruses appearing in the blood supply.

Couples who are considering having children may want to undergo genetic testing to find out if they are carriers of thalassemias or other disorders that can be passed on to children. Because people with thalassemia trait do not experience symptoms, it is possible for the trait to go undiagnosed in families, even over generations.

A complete blood count (CBC) test includes a measure of the size of a patient’s red blood cells. This is known as mean corpuscular volume (MVC). Patients with an MVC of less than 75 may be genetic carriers for thalassemia. This reading may be lower in children.

If CBC testing indicates the presence of the thalassemia gene, follow-up testing such as hemoglobin electrophoresis will be performed to confirm the finding. Confirmation testing for alpha thalassemia can be more complicated. A special DNA test called alpha globin DNA mutation analysis may be necessary. This test is only available at only a few medical centers in the United States. A patient’s physician can take a blood sample and send it to one of these centers for analysis. 

Patients with milder forms of thalassemias who do not require regular blood transfusions may need them only on certain occasions, such as during certain illnesses or during pregnancy.

Patients with severe thalassemia are vulnerable to infections that can worsen their anemia. As a result, they are urged to receive vaccinations for pneumonia and to receive annual flu shots. Patients also are urged to take folic acid supplements, as folic acid can help build red blood cells.

Preparing questions in advance can help patients and parents to have more meaningful discussions with their physicians regarding their or their child’s treatment options. The following questions related to thalassemias may be helpful:

1. How can my partner and I be tested to see if we are thalassemia carriers?
   
   
2. If we are carriers, should we decide not to have children?
   
   
3. Given our test results, what are the odds our child will have thalassemia? Which form is most likely?
   
   
4. Can you test my unborn fetus for thalassemia?
   
   
5. How is this test done? Is it painful or risky?
   
   
6. My child has thalassemia. What type of treatment will be necessary for my child?
   
   
7. What are the risks of these treatments?
   
   
8. What symptoms will my child be likely to experience?
   
   
9. How will my child’s condition impact his/her quality of life?
   
   
10. What is my child’s long-term prognosis?