What Are Thalassemias?
Thalassemias are genetic disorders that involve the decreased and defective production of hemoglobin, a molecule found inside all red blood cells (RBCs) that transports oxygen throughout the body.
As frightening as thalassemias can be, the outlook is encouraging. In the past 20 years, new therapies have greatly improved the quality of life and life expectancy in kids who have these diseases.
Thee two types of thalassemia are alpha-thalassemia and beta-thalassemia. Their names describe which part of the hemoglobin molecule that is effected, the alpha or the beta chain. Hemoglobin contains two different kinds of protein chains named alpha and beta chains. Any deficiency in these chains causes abnormalities in the formation, size, and shape of RBCs.
Thalassemia can cause ineffective production of RBCs and their destruction. As a result, people with thalassemia often have a reduced number of RBCs in the bloodstream (anemia), which can affect the transportation of oxygen to body tissues. In addition, thalassemia can cause RBCs to be smaller than normal or drop hemoglobin in the RBCs to below-normal levels.
Kids who have with different forms of thalassemia have different kinds of health problems. Some only have mild anemia with little or no effects, while others require frequent serious medical treatment.
Thalassemia is always inherited, passed on from parents to children through their genes. A child usually does not develop symptoms unless both parents carry a thalassemia gene.
If only one parent passes a gene for thalassemia on to the child, then the child is said to have thalassemia trait. Thalassemia trait will not develop into the full-blown disease, and no medical treatment is necessary.
Many families have thalassemia carriers, but the trait often goes undiagnosed because it produces no or few symptoms. Frequently, thalassemia is not diagnosed in a family until a baby is born with it. So if someone in your family carries a thalassemia gene, it's wise to have genetic counseling if you're thinking of having children.
At one time it was believed that the disease affected only people of Italian or Greek descent, but it's now known that many people with thalassemia also come from or are descended from Africa, Malaysia, China, and many parts of Southeast Asia.
Because of a recent pattern of migration from Southeast Asia, there has been an increase in the past decade of thalassemia in North America. Testing for thalassemia is generally recommended for anyone from Southeast Asia with unexplained anemia.
If your doctor determines that your child is at risk for thalassemia, prenatal tests can find out if your unborn child is affected.
Types of Thalassemias
Children with alpha-thalassemia trait do not have thalassemia disease. People normally have four genes for alpha globin, two inherited from each parent. If one or two of these four genes are affected, the child is said to have alpha-thalassemia trait.
A specific blood test called a hemoglobin electrophoresis is used to screen for alpha-thalassemia trait and can be done in infancy. Sometimes, alpha-thalassemia trait can be detected through routine newborn blood screening, which is required in most states in the U.S.
Often, results of the hemoglobin electrophoresis test are normal in people who have alpha-thalassemia trait and a diagnosis of alpha-thalassemia is done only after other conditions are ruled out and after the parents are screened. The disease can be harder to detect in older kids and adults.
Kids who have the alpha-thalassemia trait usually have no significant health problems except mild anemia, which can cause slight fatigue.
Alpha-thalassemia trait is often mistaken for an iron deficiency anemia because RBCs will appear small when viewed under a microscope.
Other cases can cause more severe anemia where three genes are affected. People with this form of alpha-thalassemia may require occasional blood transfusions during times of physical stress, like fevers or other illnesses, or when the anemia is severe enough to cause symptoms such as fatigue.
The most severe form of the disorder is called alpha-thalassemia major. This type is extremely rare, and women carrying fetuses with this form of thalassemia have a high incidence of miscarriage because the fetuses cannot survive.
Beta-thalassemia, the most common form of the disorder seen in the United States, is grouped into three categories: beta-thalassemia minor (trait), intermedia, and major (Cooley's anemia). A person who carries a beta-thalassemia gene has a 25% (1 in 4) chance of having a child with the disease if his or her partner also carries the trait.
Beta-Thalassemia Minor (trait)
Beta-thalassemia minor often goes undiagnosed because kids with the condition have no real symptoms other than mild anemia and small red blood cells. It is often suspected based on routine blood tests such as a complete blood count (CBC) and can be confirmed with a hemoglobin electrophoresis. No treatment is usually needed.
As with alpha-thalassemia trait, the anemia associated with this condition may be misdiagnosed as an iron deficiency.
Children with beta-thalassemia intermedia have varying effects from the disease — mild anemia might be their only symptom or they might require regular blood transfusions.
The most common complaint is fatigue or shortness of breath. Some kids also experience heart palpitations, also due to the anemia, and mild jaundice, which is caused by the destruction of abnormal red blood cells that result from the disease. The liver and spleen may be enlarged, which can feel uncomfortable for a child. Severe anemia can also affect growth.
Another symptom of beta-thalassemia intermedia can be bone abnormalities. Because the bone marrow is working overtime to make more RBCs to counteract the anemia, kids can experience enlargement of their cheekbones, foreheads, and other bones. Gallstones are a frequent complication because of abnormalities in bile production that involve the liver and the gallbladder.
Some kids with beta thalassemia intermedia may require a blood transfusion only occasionally. They will always have anemia, but may not need transfusions except during illness, medical complications, or later on during pregnancy.
Other children with this form of the disease require regular blood transfusions. In these kids, low or falling hemoglobin levels greatly reduce the blood's ability to carry oxygen to the body, resulting in extreme fatigue, poor growth, and facial abnormalities. Regular transfusions can help alleviate these problems. Sometimes, kids who have this form of the disease have their spleens removed.
Beta-thalassemia intermedia is often diagnosed in the first year of life. Doctors may be prompted to test for it when a child has chronic anemia or a family history of the condition. As long as it is diagnosed while the child is still doing well and has not experienced any serious complications, it can be successfully treated and managed.
Beta-thalassemia major, also called Cooley's anemia, is a severe condition in which regular blood transfusions are necessary for the child to survive.
Although multiple lifelong transfusions save lives, they also cause a serious side effect: an overload of iron in the bodies of thalassemia patients. Over time, people with thalassemia accumulate deposits of iron, especially in the liver, heart, and endocrine (hormone-producing) glands. The deposits eventually can affect the normal functioning of the heart, and liver, in addition to delaying growth and sexual maturation.
To minimize iron deposits, kids must undergo chelation (iron-removing) therapy. This can be done by taking daily medication by mouth or by subcutaneous or intravenous administration.
Daily chelation therapy is given 5 to 7 days a week and has been proven to prevent liver and heart damage from iron overload, allow for normal growth and sexual development, and increase life span. Iron concentrations are monitored every few months. Sometimes liver biopsies are needed to get a more accurate picture of the body's iron load.
Children on regular transfusions are monitored closely for iron levels and complications of iron overload on the chelation medications.
Other risks associated with chronic blood transfusions for thalassemia major include blood-borne diseases like hepatitis B and C. Blood banks screen for such infections, in addition to rarer infections such as HIV. In addition, kids who have many transfusions can develop allergic reactions that can prevent further transfusions and cause serious illnesses.
For kids and teens with thalassemia, adolescence can be a difficult time, particularly because of the amount of time required for transfusions and chelation therapy.
Recently, some kids have successfully undergone bone marrow transplants to treat thalassemia major; however, this is considered only in cases of severely disabling thalassemia disease. There is considerable risk to bone marrow transplants: the procedure involves the destruction of all of the blood-forming cells in the bone marrow and repopulating the marrow space with donor cells that must match perfectly (the closest match is usually from a sibling).
The procedure is usually done in children younger than 16 years of age who have no existing evidence of liver scarring or serious liver disease. Results have been encouraging so far, with disease-free survival in many patients.
Blood-forming stem cells taken from umbilical cord blood have also been successfully transplanted, and research using this technique is expected to increase. Currently bone marrow treatment is the only known cure for the disease.
Talking to the Doctor
If you know the thalassemia trait exists in your family, it's important to meet with your doctor, particularly if you notice any of the symptoms of thalassemia major — anemia, listlessness, or bone abnormalities — in your child.
If you're thinking of having children, speak with a genetic counselor to determine your risk of passing on the disease.
Reviewed by: Robin Miller, MD
Date reviewed: November 2008