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. 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 alpha chain genes located on each #16 chromosome, for a total of 4. 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 child:

alpha thalassemia major - all four alpha chain genes are deleted, which is so severe that death can occur in utero (prior to birth).
alpha thalassemia carrier - two alpha chain genes are deleted, either:
- both from the same #16 chromosome, called a "cis deletion"
- one from both #16 chromosomes, called a "trans deletion"
  When 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 thal major. Carriers of the cis deletion versus the trans deletion can be distinguished by DNA analysis only. DNA testing is usually done from a blood sample, to look 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 has only one functioning alpha chain gene, resulting in a hemolytic anemia that can worsen with febrile illness or exposure to certain drugs, chemicals, or infectious agents. Persons with hemoglobin H disease are at increased risk to have a child with alpha thal 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 and 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 determined 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.