What Your Test Results Mean:

There are two types of alpha thalassemia carriers, alpha thalassemia silent carriers and individuals with alpha thalassemia trait. Silent carriers have no symptoms while individuals with alpha thalassemia trait may be identified to have mild anemia in the presence of normal iron levels. All carriers are at an increased risk of having a child with alpha thalassemia. Risk for the current or future pregnancies is dependent on your partner’s carrier status.

Disease Explained:

Alpha thalassemia is an inherited disorder caused by decreased synthesis of hemoglobin alpha chain, a protein in the red blood cells required for oxygen delivery. There are four types of alpha thalassemia—Hb Bart syndrome, Hb H disease, alpha thalassemia trait, and silent carrier. In the most severe type, Hb Bart syndrome, pregnancies may result in stillbirth or early infant death. Anemia, enlargement of the spleen and liver, mild jaundice, skeletal changes, particularly in the face, are general features of Hb H disease. Individuals with alpha thalassemia trait may have mild anemia in the presence of normal iron levels while alpha thalassemia silent carriers are clinically normal.

Management of Hb Bart syndrome is focused on care of the mother during pregnancy as well as supportive care in infancy as it is typically a fatal disease. Individuals with Hb H disease require annual follow up with a hematologist and may require red blood cell transfusions. Other complications, such as splenomegaly, gallstones, and leg ulcers, may require appropriate medical or surgical treatment. Silent carriers and individuals with alpha thalassemia trait typically require no medical management.

How the Genetics Works:

The clinical features of alpha thalassemia can be explained by deletions or pathogenic variants in the HBA1 or HBA2 alpha-globin genes. All individuals have two copies of the HBA1 and HBA2 genes, for a total of four genes encoding for the alpha chain component of hemoglobin in red blood cells. Individuals who are silent carriers have lost one of the alpha-globin genes (α-/ αα) and are clinically normal, whereas individuals with alpha thalassemia trait have lost two copies of the alpha-globin genes either in cis or in trans, (α-/α-) or (–/αα.) and may have mild anemia. Individuals with Hb H disease have lost three of the alpha-globin genes (α-/αα). In the most severe type of alpha thalassemia, Hb Bart syndrome, all four alpha-globin genes are lost (–/–).