Red blood cell hemoglobin is used to transport oxygen from the lungs to the tissues. It consists of one pair of alpha chains and one pair of beta chains. Hemoglobin H (Hb H) is an abnormal and dysfunctional hemoglobin composed solely of beta chains. Hb H is present when alpha chain synthesis is insufficient. The gene responsible for alpha chain synthesis is present in two copies on the chromosomes. Individuals who have two copies of the mutated gene (homozygous) will have very low production of normal alpha chains (homozygous for alpha thalassemia). Individuals with a single mutated copy (heterozygous or alpha thalassemia “trait carriers”) will have NEAR-NORMAL alpha chain synthesis and will have few or no symptoms (silent alpha thalassemia or alpha thalassemia minor). The most severe form of alpha thalassemia is very rare in North America.
Carriers of the alpha thalassemia trait have small, pale red blood cells and have little or no anemia. In the most severe cases (homozygous), patients have a high level of hemoglobin H with moderate hemolytic anemia and a sometimes severely enlarged spleen (splenomegaly). A diagnosis of alpha thalassemia is usually confirmed by molecular testing (DNA analysis).