Alpha Thalassemia

What is alpha thalassemia?

Thalassemia is an inherited disorder that affects the production of normal hemoglobin (a type of protein in red blood cells that carries oxygen to the tissues of the body). Thalassemia includes a number of different forms of anemia, including the alpha thalassemias. The severity and type of anemia depends upon the number of genes that are affected.

What causes alpha thalassemia?

Alpha thalassemia is caused by mutations in the alpha chain of the hemoglobin molecule. Normally, there are two genes coding for the alpha chain on each #16 chromosome, for a total of four genes. The alpha chain is an important component of fetal hemoglobin (which is usually made before birth) and hemoglobin A and hemoglobin A2 (which are present after birth). How these genes are altered determines the specific type of alpha thalassemia in a person:

Alpha thalassemia major. All four alpha chain genes are deleted. This results in an anemia that is so severe that death usually occurs in utero (prior to birth).
Alpha thalassemia carrier. Two alpha chain genes are deleted. If both deleted genes are from the same #16 chromosome, it is called a "cis deletion" and is inherited from one parent. If instead one gene is missing from both #16 chromosomes, it is called a "trans deletion" and is inherited from both parents. This results in an anemia that is usually mild to moderate, but can be severe. When both parents are carriers of the cis deletion, there is a one in four, or 25 percent, chance with each pregnancy, to have a baby with alpha thalassemia major. Identifying whether an alpha thalassemia carrier has the cis deletion versus two trans deletions requires testing by DNA (deoxyribonucleic acid) analysis. DNA testing is usually done from a blood sample, and looks at the alpha chain genes on each #16 chromosome, to determine which are deleted.
Hemoglobin H disease. Three alpha chain genes are deleted. Hemoglobin H disease occurs when a person inherits a cis deletion from one parent and a trans deletion from the other so that they have only one functioning alpha chain gene, resulting in a severe hemolytic anemia that can worsen with febrile illness or exposure to certain drugs, chemicals, or infectious agents, and often requires blood transfusions. Persons with hemoglobin H disease are at increased risk to have a child with alpha thalassemia major, since they carry one #16 chromosome with an alpha chain two gene deletion (cis deletion).
Silent alpha thalassemia carrier. One alpha chain gene is deleted (the other three are normal). Blood tests are usually normal, though the red cells may be small, leading to a suspicion that the patient is a silent carrier. The only way to confirm a silent carrier is by DNA studies.

How is alpha thalassemia diagnosed?

Alpha thalassemia is most commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and the Mediterranean region. Carrier status can be suggested by the following:

Complete blood count (CBC). A measurement of size, number, and maturity of different blood cells in a specific volume of blood.
Hemoglobin electrophoresis with A2 and F quantitation. A lab procedure that differentiates the types of hemoglobin present.
FEP (free-erythrocyte protoporphyrin) and ferritin. To exclude iron-deficiency anemia

All of these studies can be performed from a single blood sample. Prenatal diagnosis is determined from CVS (chorionic villus sampling) or amniocentesis. Confirmation of alpha thalassemia requires DNA analysis.