Alpha Thalassemia Facts*
*Alpha thalassemia facts medical author: Melissa Conrad Stöppler, MD
- Alpha thalassemia is a blood disorder that reduces the production of normal hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body.
- There are four types of alpha thalassemia, hemoglobin Bart hydrops fetalis
syndrome or Hb Bart syndrome (the more severe form), HbH disease, silent carrier
state and trait.
- Alpha thalassemia occurs frequently in people from Mediterranean countries, North Africa, the Middle East, India, and Central Asia.
- Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes.
- People who have alpha thalassemia trait can have mild anemia. However, many people with this type of thalassemia have no signs or symptoms.
- Treatments for thalassemias depend on the type and severity of the disorder.
What is alpha thalassemia?
Alpha thalassemia is a blood disorder that reduces the production of normal hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body.
What are the symptoms of alpha thalassemia?
In people with the characteristic features of alpha thalassemia, a reduction in the amount of
normal hemoglobin prevents enough oxygen from reaching the body’s tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.
Alpha Thalassemia Testing
Is there a test for thalassemia?
Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier. If both parents are carriers, they may want to consult with a genetic counselor for help in deciding whether to conceive or whether to have a fetus tested for thalassemia.
Prenatal testing can be done around the 11th week of pregnancy using chorionic villi sampling (CVS). This involves removing a tiny piece of the placenta. Or, the fetus can be tested with amniocentesis around the 16th week of pregnancy. In this procedure, a needle is used to take a sample of the fluid surrounding the baby for testing.
Assisted reproductive therapy is also an option for carriers who don’t want to risk giving birth to a child with thalassemia. A new technique, pre-implantation genetic diagnosis (PGD), used in conjunction with in vitro fertilization, may enable parents who have thalassemia or carry the trait to give birth to healthy babies. Embryos created in-vitro are tested for the thalassemia gene before being implanted into the mother, allowing only healthy embryos to be selected.
SOURCE: National Heart Lung and Blood Institute
What are the types of alpha thalassemia?
Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome. The milder form is called HbH disease.
Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. As a result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.
HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice).
Some affected individuals also have bone changes such as overgrowth of the upper
jaw and an unusually prominent forehead. The features of HbH disease usually
appear in early childhood, but affected individuals typically live into adulthood.
How Common Is Alpha Thalassemia?
Alpha thalassemia is a fairly common blood disorder worldwide. Thousands of infants with Hb Bart syndrome and HbH disease are born each year, particularly in Southeast Asia. Alpha thalassemia also occurs frequently in people from Mediterranean countries, North Africa, the Middle East, India, and Central Asia.
Sickle cell disease is named after a farming tool.
What Genes Are Related to Alpha Thalassemia
Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes. Both of these genes provide instructions for making a protein called alpha-globin, which is a component (subunit) of hemoglobin.
People have two copies of the HBA1 gene and two copies of the HBA2 gene in each cell. Each copy is called an allele. For each gene, one allele is inherited from
the father, and the other is inherited from the mother. As a result, there are four alleles that produce alpha-globin. The different types of alpha thalassemia result from the loss of some or all of these alleles.
Hb Bart syndrome, the most severe form of alpha thalassemia, results from the loss of all four alpha-globin alleles. HbH disease is caused by a loss of three of the four alpha-globin alleles. In these two conditions, a shortage of alpha-globin prevents cells from making normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin called hemoglobin Bart (Hb Bart) or hemoglobin H (HbH). These abnormal hemoglobin molecules cannot effectively carry oxygen to the body’s tissues. The substitution of Hb Bart or HbH for normal hemoglobin causes anemia and the other serious health problems associated with alpha thalassemia.
Two additional variants of alpha thalassemia are related to a reduced amount of alpha-globin.
However, cells still produce some normal hemoglobin, these variants tend to cause few or no health problems,
and the loss of two of the four alpha-globin alleles results in alpha thalassemia trait. People with alpha thalassemia trait may have unusually small, pale red blood cells and mild anemia. A loss of one alpha-globin allele is found in alpha thalassemia silent carriers. These individuals typically have no thalassemia-related signs or symptoms.
How Do People Inherit Alpha Thalassemia?
The inheritance of alpha thalassemia is complex. Each person inherits two alpha-globin alleles from each parent. If both parents are missing at least one alpha-globin allele, their children are at risk of having Hb Bart syndrome, 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.