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California Newborn Screening Program

Alpha Thalassemia

Types of Alpha Thalassemia

  • Alpha thalassemia major (Hydrops Fetalis): Deletion of all four alpha globin genes. No alpha chains, which are necessary for the formation of fetal hemoglobin, are produced. Death usually occurs in utero or early infancy. Treatment consists of ongoing transfusions.
  • Hemoglobin H (Hb H) disease: Deletion of three alpha globin genes. The clinical complications associated with Hb H disease are variable. This generally results in mild to moderate anemia, and is often associated with microcytosis, hypochromia, and red cell fragmentation.

Hemoglobin H is an abnormal hemoglobin found in people with alpha thalassemia. When three or more alpha globin genes malfunction, there is an excess of beta globin chains. The excess chains create unstable tetramers called hemoglobin H. The tetramer of beta globin chains forms when there are insufficient alpha chains to make normal adult hemoglobin. The fetus manufactures gamma chains rather than beta chains, and the tetramer of gamma chains that forms is called hemoglobin Barts. During the newborn period, when gamma globin production is still high and beta globin production is low, the gamma chains form the unstable tetramers identified as hemoglobin Barts. However, hemoglobin Barts decreases with the normal decrease in gamma chain production and therefore, over time, it disappears and is replaced by Hb H. These unstable tetramers eventually precipitate in the red blood cells, causing membrane damage and premature destruction of the cells producing a chronic hemolytic anemia. It is the identification of large amounts of Hb Barts that leads us to presume the infant will have Hb H disease. DNA testing is necessary to make the final diagnosis.

  • Hemoglobin H (Hb H)-Constant Spring disease: Deletion of two alpha globin genes and a point mutation of a third. This is generally a more severe form of Hb H disease, usually with a moderate to severe clinical course. Complications include the development of splenomegaly and cholelithiasis. Some individuals may require intermittent to chronic transfusions.

Clinical symptoms for both forms of Hb H disease that can begin at birth include pallor and jaundice. In addition, severe anemia may be caused by certain types of medications (including aspirin, sulfa drugs, some antibacterials) as well as fava beans and mothballs. Avoidance of these substances is recommended. Detailed list of substances to avoid

Alpha thalassemia trait (also called alpha thalassemia minor): Deletion of two alpha globin genes. This condition is clinically benign. The clinical manifestations include microcytosis and mild, if any, anemia, which is often confused with iron deficiency anemia. However, unless the individual also has iron deficiency anemia, iron supplementation is usually not recommended. People with alpha thalassemia trait may be at risk for having a child with Hb H disease or alpha thalassemia major.

  • Alpha thalassemia "silent carrier": Deletion of one alpha globin gene. This condition is clinically benign, usually with no clinical manifestations.

What is the Treatment for Hemoglobin H Disease?

The child's doctor or blood specialist should be notified whenever the child becomes ill, so any infection can be promptly treated. If the anemia becomes severe, the child may need a blood transfusion. The doctor will discuss which medications to avoid. Extra amounts of a vitamin called folic acid may be given to the child. Parents should not have mothballs or fava beans in the home. The blood specialist will discuss how to care for the child, and what symptoms of severe anemia to watch for. Most people with Hb H disease can lead relatively normal lives with proper treatment.


Last modified on: 8/23/2010 2:13 PM