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.
Alpha-thalassemia has two types that can cause health problems: the more severe type is known as Hb Bart syndrome; the milder form is called HbH disease. Hb Bart syndrome may be characterized by hydrops fetalis; severe anemia; hepatosplenomegaly; heart defects; and abnormalities of the urinary system or genitalia. Most babies with this condition are stillborn or die soon after birth. HbH disease may cause mild to moderate anemia; hepatosplenomegaly; jaundice; or bone changes. No treatment is effective for Hb Bart syndrome. For HbH disease, occasional red blood cell transfusions may be needed.
Alpha-thalassemia typically results from deletions involving the HBA1 and HBA2 genes. Four genes are involved in making the alpha hemoglobin chain. You get two from each of your parents. If you inherit:
- One mutated gene, you'll have no signs or symptoms of thalassemia. But, you are a carrier of the disease and can pass it on to your children.
- Two mutated genes, your thalassemia signs and symptoms will be mild. This condition may be called alpha-thalassemia minor, or you may be told you have an alpha-thalassemia trait.
- Three mutated genes, your signs and symptoms will be moderate to severe. This condition is also called hemoglobin H disease.
- Four mutated genes, the condition is called alpha-thalassemia major or hydrops fetalis. It usually causes a fetus to die before delivery or a newborn to die shortly after birth.
The severity of symptoms depends on the severity of the disorder.
• No Symptoms: Alpha thalassemia silent carriers generally have no signs or symptoms of the disorder. The lack of alpha globin protein is so minor that the body's hemoglobin works normally.
• Mild Anemia: People who have alpha trait can have mild anemia. However, many people who have these types of thalassemia have no signs or symptoms. Mild anemia can make you feel tired. Mild anemia caused by alpha thalassemia trait might be mistaken for iron-deficiency anemia.
• Severe Anemia and other Signs and Symptoms People who have hemoglobin H disease have severe thalassemia. Signs and symptoms usually occur within the first 2 years of life. They may include severe anemia and other health problems, such as:
- A pale and listless appearance
- Poor appetite
- Dark urine (a sign that red blood cells are breaking down)
- Slowed growth and delayed puberty
- Jaundice (a yellowish color of the skin or whites of the eyes)
- An enlarged spleen, liver, or hear
- Bone problems (especially with bones in the face)
- Pale appearance
- Yellow discoloration of skin (jaundice)
- Facial bone deformities
- Abdominal swelling
- Abnormality of the heme biosynthetic pathway
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.
The inheritance of alpha-thalassemia is complex because the condition involves two genes: HBA1 and HBA2. People have two copies of the HBA1 gene and two copies of the HBA2 gene in each cell. Each copy is called an allele. Therefore, there are 4 alleles that produce alpha-globin, the protein that results from these genes. For each of the 2 genes, one allele is inherited from a person's father, and the other is inherited from a person's mother - so each person inherits 2 alleles from each parent. The different types of alpha-thalassemia result from the loss of some or all of these alleles.
If both parents are missing at least one alpha-globin allele, each of their children are at risk of having Hb Bart syndrome or hydrops fetalis, hemoglobin H (HbH) disease, or alpha-thalassemia trait. The precise risk depends on how many alleles are missing and which combination of the HBA1 and HBA2 genes is affected.
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 a 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 genes
If a history of this disease in your family exists, should consider to do prenatal tests.
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 fetus.
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.
- For silent carriers and individuals with alpha thalassemia trait, the prognosis is excellent.
- For individuals with hemoglobin H disease, the overall survival rate varies but is generally good, with most patients surviving into adulthood. However, some patients have a more complicated course and may not do as well.
- Hydrops fetalis (alpha thalassemia major) is incompatible with life and requires identification in utero and in utero transfusions if the fetus is to survive and be born. To identify fetuses with this condition, family genetic studies must be done, high-risk couples identified, and the fetus tested in utero for the absence of alpha-globin chains.
Treatment of alpha-thalassemia often includes blood transfusions to provide healthy blood cells that have normal hemoglobin. Bone marrow transplant has helped to cure a small number of individuals with severe alpha-thalassemia.
- Deferasirox (Exjade) is indicated for the treatment of chronic iron overload in alpha-thalassemia.
- Deferiprone (Ferriprox) is indicated in the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate
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