Alpha Thalassemia

What is alpha thalassemia?

Alpha thalassemia is a type of thalassemia that is inherited (passed down through families). It is a blood disorder that reduces how well the body produces healthy red blood cells and normal hemoglobin. Hemoglobin is an iron-rich protein in red blood cells that carries oxygen to cells throughout the body. There are two parts of this protein – one is called alpha globin and one is called beta globin.

Certain genes control how the body makes hemoglobin. When these genes are altered (changed) or missing, thalassemia occurs. The hemoglobin protein affected in alpha thalassemia is the alpha globin.

People who inherit hemoglobin genes that are altered or missing from one parent but inherit normal genes from the other parent are called carriers. Carriers of alpha thalassemia usually have no signs or symptoms. However, they can pass the faulty genes on to their children. People who have moderate to severe forms of alpha thalassemia have inherited faulty hemoglobin genes from both parents.

Alpha globin is made by four specific genes—two on each strand of chromosome 16. Each person needs these four genes (two from each parent) to make enough alpha globin for the body’s hemoglobin to work normally. Different forms of alpha thalassemia occur if one or more of these genes are missing:

• If one gene is missing—a person is a “silent” carrier of alpha thalassemia and usually has no signs or symptoms.
• If two genes are missing—a person has alpha thalassemia trait (also called alpha thalassemia minor) and may have mild anemia.
• If three genes are missing—a person has hemoglobin H disease. This can cause moderate to severe anemia.
• If all four genes are missing—a person has alpha thalassemia major (also called hemoglobin Bart’s or hydrops fetalis). This is the most severe type of alpha thalassemia. A fetus with this disorder will usually die in the womb or the baby will die soon after birth because the child is unable to make normal hemoglobin to carry oxygen throughout the body.

How common is alpha thalassemia?

Because alpha thalassemia is inherited, family history and ancestry can help diagnose this blood disorder.

A parent with alpha globin-making genes that are altered or missing, may have a child with a form of alpha thalassemia. Each child has a 25 percent chance of inheriting one, two or three missing genes. A baby born without all four genes is very rare.

Alpha thalassemia is one of the most common blood disorders in the world. Anyone can have alpha thalassemia. Thousands of infants are born with alpha thalassemia trait or hemoglobin H disease each year, but it is most common in Southeast Asia. It also occurs often in people of African, Greek, Italian and Middle Eastern descent.

What are the signs and symptoms of alpha thalassemia?

Signs and symptoms of alpha thalassemia are caused by a lack of oxygen being carried throughout the body. This occurs because the body does not make enough healthy red blood cells and alpha globin.

How severe the signs or symptoms are depends on the type of alpha thalassemia a person has and the severity of the disorder:

• No symptoms—Silent carriers of alpha thalassemia generally have no signs or symptoms of the disorder. The body’s hemoglobin works normally because the lack of alpha globin protein is minor.
• Mild anemia—People with alpha thalassemia trait may have no signs or symptoms, but mild anemia is common:
  • Feeling tired or weak 
  • Shortness of breath
  • Feeling dizzy
  • Headache
  • Cold hands and feet
  • Pale skin
  • Chest pain

• Moderate to severe anemia and other health problems—People with advanced forms of alpha thalassemia (hemoglobin H disease) will usually have signs or symptoms within the first two years of life, including moderate to severe anemia and other health issues:
  • Pale skin and listless
  • Poor appetite
  • Dark urine
  • Slowed growth and delayed puberty
  • Yellowish skin or whites of the eyes (jaundice)
  • Enlarged heart, liver or spleen
  • Bone problems
  • Hydrops fetalis must be diagnosed in utero. The fetus usually does not survive, although on rare occasions a fetus can be transfused in utero and survive. 

How is alpha thalassemia treated?

Treatment is based on the type and severity of alpha thalassemia. People who are carriers of alpha thalassemia or have alpha thalassemia trait usually have mild or no symptoms and need little or no treatment. The symptoms for people with hemoglobin H disease vary depending on the type of alpha thalassemia. People with hydrops fetalis must depend on transfusions their entire lives and have severe health problems. 

Several standard treatments are used for moderate and severe forms of the disorder: 

• Blood transfusions—are the main treatment for people with severe alpha thalassemia. This treatment provides healthy red blood cells with normal hemoglobin.
  • Because red blood cells only live about three months, repeated transfusions may be needed to maintain a healthy supply of red blood cells.
  • People with hemoglobin H disease may need a blood transfusion on occasion, such as during an infection or other illness or if symptoms of anemia occur.
  • Blood transfusions are a life-saving treatment that can help people with alpha thalassemia feel better, live longer and have better quality of life overall. But transfusions increase the risk of transmitted infections and viruses such as hepatitis. Careful blood screening occurs in the United States, which makes this risk much lower.
• Iron chelation therapy—removes excess iron from the body caused by repeated blood transfusions, which are a treatment for severe alpha thalassemia. Buildup of iron in the blood (iron overload) can damage the heart, liver and other parts of the body. Two drugs are used for chelation therapy:
  • Deferoxamine—a liquid medicine given slowly under the skin, usually overnight, five to six nights a week, with a small, portable pump. This treatment takes time and can be mildly painful. Side effects may include problems with hearing and vision.
  • Deferasirox—an oral drug taken by mouth once a day. Side effects may include headache, nausea, vomiting, diarrhea, tiredness and joint pain.

Used much less often, these other treatments for alpha thalassemia exist or are being explored:

• Blood and bone marrow stem cell transplant—replaces faulty stem cells with healthy ones from a donor.
  • Stem cells are the cells inside bone marrow that become red blood cells and other types of blood cells.
  • A stem cell transplant is the only treatment that can cure alpha thalassemia, but the procedure has some risks.
  • Only a small percentage of people with severe alpha thalassemia are able to be matched well with a donor.
• Future treatments—Researchers are working to find possible new treatments for alpha thalassemia. 
  • By using gene therapy, someday it might be possible for doctors to insert a normal hemoglobin gene into stem cells in bone marrow. This might allow people with alpha thalassemia to make their own healthy hemoglobin and red blood cells.
  • Scientists are studying ways to trigger the body’s ability to make fetal hemoglobin after birth. The body switches to making adult hemoglobin when a baby is born. So, making more fetal hemoglobin might help replace the lack of healthy adult hemoglobin in people with alpha thalassemia.

What are the survival rates for alpha thalassemia?

Treatment for hemoglobin H has improved, and people with a moderate or severe form of the disorder are living longer with better quality of life. However, health problems caused by alpha thalassemia and its treatment are common and can be serious. 

Severe thalassemia (severe hemoglobin H or hydrops fetalis) can cause heart failure and death. Regular blood transfusions and iron chelation therapy or a successful stem cell transplant may improve the chance of survival. 

Less severe forms of alpha thalassemia (silent carrier or alpha thalassemia trait) usually do not shorten the person’s lifespan.

Genetic counseling and prenatal screening may help people with a family history of alpha thalassemia that plan to have children.

Why choose St. Jude for your child’s alpha thalassemia treatment?

• The nurse-to-patient ratio at St. Jude is unmatched—averaging 1:3 in hematology and oncology, and 1:1 in the Intensive Care Unit.
• The hospital’s major treatment programs are so successful because the doctors and laboratory scientists work closely together to quickly develop new therapies.