Thalassemia is an inherited blood disorder that reduces the production of functional hemoglobin (the protein in red blood cells that carries oxygen). This causes a shortage of red blood cells and low levels of oxygen in the bloodstream, leading to a variety of health problems. There are two main types of thalassemia: alpha thalassemia and beta thalassemia.
Beta thalassemia is caused by mutations in the HBB gene while alpha thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. Both are inherited in an autosomal recessive manner. which means that two copies of the gene are necessary to produce the condition, one inherited from each parents. Treatment depends on the type and severity of the condition but may include blood transfusions and/or folic acid supplements. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.
While two genes are involved in making the beta hemoglobin chain. If you inherit:
- One mutated gene, you'll have mild signs and symptoms. This condition is called beta-thalassemia minor or referred to as a beta-thalassemia trait.
- Two mutated genes, your signs and symptoms will be moderate to severe. This condition is called beta-thalassemia major, which is also known as Cooley's anemia. Babies born with two defective beta hemoglobin genes usually are healthy at birth, but develop signs and symptoms within the first two years of life. A milder form, called beta-thalassemia intermedia, also may occur with two mutated genes.
The signs and symptoms vary depending on the severity of the thalassemia. Symptoms may include:
- Sever anemia
- Pale appearance
- Yellow discoloration of skin (jaundice)
- Facial bone deformities
- Slow growth
- Abdominal swelling
- Dark urine
The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Some adolescents with thalassemia major experience delayed puberty.
Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities.
Possible complications of thalassemia include:
- Iron overload. People with thalassemia can get too much iron in their bodies, either from the disease itself or from frequent blood transfusions. Too much iron can result in damage to your heart, liver and endocrine system, which includes glands that produce hormones that regulate processes throughout your body.
- Infection. People with thalassemia have an increased risk of infection. This is especially true if you've had your spleen removed.
In cases of severe thalassemia, the following complications can occur:
- Bone deformities. Thalassemia can make your bone marrow expand, which causes your bones to widen. This can result in abnormal bone structure, especially in your face and skull. Bone marrow expansion also makes bones thin and brittle, increasing the chance of broken bones.
- Enlarged spleen (splenomegaly). The spleen helps your body fight infection and filter unwanted material, such as old or damaged blood cells. Thalassemia is often accompanied by the destruction of a large number of red blood cells, making your spleen work harder than normal, causing your spleen to enlarge. Splenomegaly can make anemia worse, and it can reduce the life of transfused red blood cells. If your spleen grows too big, it may need to be removed.
- Slowed growth rates. Anemia can cause a child's growth to slow. Puberty also may be delayed in children with thalassemia.
- Heart problems. Heart problems, such as congestive heart failure and abnormal heart rhythms (arrhythmias), may be associated with severe thalassemia.
Mutations in the HBB gene cause beta thalassemia. The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of hemoglobin. Hemoglobin consists of four protein subunits, typically two subunits of beta-globin and two subunits of another protein called alpha-globin.
Some mutations in the HBB gene prevent the production of any beta-globin. The absence of beta-globin is referred to as beta-zero (B0) thalassemia. Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (B+) thalassemia. Having either B0 or B+ thalassemia does not necessarily predict disease severity, however; people with both types have been diagnosed with thalassemia major and thalassemia intermedia.
A lack of beta-globin leads to a reduced amount of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. The low number of mature red blood cells leads to anemia and other associated health problems in people with beta thalassemia.
Thalassemia major and thalassemia intermedia are inherited in an autosomal recessive pattern, which means both copies of the HBB gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Sometimes, however, people with only one HBB gene mutation in each cell develop mild anemia. These mildly affected people are said to have thalassemia minor.
In a small percentage of families, the HBB gene mutation is inherited in an autosomal dominant manner. In these cases, one copy of the altered gene in each cell is sufficient to cause the signs and symptoms of beta thalassemia.
In most cases, thalassemia can't be prevented. If you have thalassemia, or if you carry a thalassemia gene, consider talking with a genetic counselor for guidance before you have or father a child
Most children with moderate to severe thalassemia show signs and symptoms within their first two years of life. If your doctor suspects your child has thalassemia, he or she may confirm a diagnosis using blood tests. If your child has thalassemia, blood tests may reveal:
- A low level of red blood cells
- Smaller than expected red blood cells
- Pale red blood cells
- Red blood cells that are varied in size and shape
- Red blood cells with uneven hemoglobin distribution, which gives the cells a bull's-eye appearance under the microscope
Blood tests may also be used to:
- Measure the amount of iron in your child's blood
- Evaluate his or her hemoglobin
- Perform DNA analysis to diagnose thalassemia or to determine if a person is carrying mutated hemoglobin gene.
Testing can be done before a baby is born to find out if it has thalassemia and determine how severe it may be. Tests used to diagnose thalassemia in fetuses include:
- Chorionic villus sampling. This test is usually done around the 11th week of pregnancy and involves removing a tiny piece of the placenta for evaluation.
- Amniocentesis. This test is usually done around the 16th week of pregnancy and involves taking a sample of the fluid that surrounds the fetes
Assisted reproductive technology
A form of assisted reproductive technology that combines pre-implantation genetic diagnosis with in vitro fertilization may help parents who have thalassemia or who are carriers of a defective hemoglobin gene give birth to healthy babies. The procedure involves retrieving mature eggs from a woman and fertilizing them with a man's sperm in a dish in a laboratory. The embryos are tested for the defective genes, and only those without genetic defects are implanted in the woman
The thalassemia disorders occur most often among people of Italian, Greek, Middle Eastern, Southern Asian, and African descent. Severe forms are usually diagnosed in early childhood and are lifelong conditions.
Individuals with thalassemia minor (thalassemia trait) usually have mild, asymptomatic microcytic anemia. This state does not result in mortality or significant morbidity.
The prognosis of patients with thalassemia major is highly dependent on the patient's adherence to long-term treatment programs, namely the hypertransfusion program and lifelong iron chelation. Allogeneic bone marrow transplantation may be curative.
Factors that increase your risk of thalassemia include:
- Family history of thalassemia. Thalassemia is passed from parents to children through mutated hemoglobin genes. If you have a family history of thalassemia, you may have an increased risk of the condition.
- Certain ancestry. Thalassemia occurs most often in people of Italian, Greek, Middle Eastern, Asian and African ancestry.
T. Major (moderate to severe thalassemia ) may include:
- Frequent blood transfusions. More-severe forms of thalassemia often require frequent blood transfusions, possibly every few weeks. Over time, blood transfusions cause a buildup of iron in your blood, which can damage your heart, liver and other organs. To help your body get rid of the extra iron, you may need to take medications that rid your body of extra iron.
- Stem cell transplant. Also called a bone marrow transplant, a stem cell transplant may be used to treat severe thalassemia in select cases. Prior to a stem cell transplant, you receive very high doses of drugs or radiation to destroy your diseased bone marrow. Then you receive infusions of stem cells from a compatible donor. However, because these procedures have serious risks, including death, they're generally reserved for people with the most severe disease who have a well-matched donor available — usually a sibling.
T. intermedia (milder form of T. major)
Some people with beta-thalassemia intermedia may need treatment for iron overload.
- Deferiprone (Ferriprox) is indicated in the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate
T. Minor (little to mild thalassemia)
Signs and symptoms are usually mild with thalassemia minor and little, if any, treatment is needed. Occasionally, you may need a blood transfusion, particularly after surgery, after having a baby or to help manage thalassemia complications.