Clinical Information

Alpha-globin gene sequencing detects alpha-globin variants and nondeletional alpha-thalassemia variants.

Alpha thalassemia is the most common monogenic condition in the world. It is estimated that up to 5% of the world's population carries at least one alpha-thalassemia variant, and in the United States, approximately 30% of African Americans are thought to carry an alpha-thalassemia variant. Alpha-thalassemia variants are most common in individuals of Southeastern Asian, African, Mediterranean, Indian, and Middle Eastern descent, but they can be found in persons from any ethnic group.

Four alpha-globin genes are normally present, 2 copies on each chromosome 16. Alpha-thalassemia variants result in decreased alpha-globin chain production. In general, alpha thalassemia is characterized by hypochromic, microcytic anemia and varies clinically from asymptomatic (alpha-thalassemia silent carrier and alpha-thalassemia trait) to lethal hemolytic anemia (hemoglobin [Hb] Barts hydrops fetalis).

Large deletions of the alpha-globin genes account for approximately 90% of alpha-thalassemia alterations, and these will not be detected by alpha-globin gene sequencing. Other alterations, such as point alterations or small deletions within the alpha-globin genes, account for most of the remaining 10% of alpha-thalassemia variants. These nondeletional subtypes can be detected by alpha-globin gene sequencing. The most common nondeletional alpha-thalassemia variant is Hb Constant Spring.

The majority of alpha-globin chain variants are clinically and hematologically benign; however, some cause erythrocytosis and chronic hemolytic anemia. Hemoglobin electrophoresis may not be able to confirm their identity. In these instances, alpha-globin gene sequencing can be useful.