Alpha Thalassemia Carrier Screening

This test is designed to detect carriers of alpha thalassemia. Alpha thalassemia refers to a group of blood disorders that results from deficiency of functional hemoglobin typically due to decrease in the production of alpha globin chains. Individuals generally have four copies of the alpha globin genes (2 copies of HBA1 and 2 copies of HBA2). Silent carriers of alpha-thalassemia have three functional copies of the alpha globin genes and are not expected to manifest symptoms. Individuals with alpha thalassemia trait have two functional copies of the alpha globin gene and may have mild anemia which cannot be treated with iron. The clinically significant forms of alpha thalassemia are hemoglobin H (HbH) disease and hemoglobin Bart hydrops fetalis (Hb Bart) syndrome. Hemoglobin H disease occurs (MIM 613978) in individuals with only one functional copy of the alpha globin genes. HbH disease usually presents in early childhood and symptoms include hemolytic anemia, splenomegaly, mild jaundice, and bone changes. Hb Bart syndrome (MIM 236750) is a severe disorder which occurs when no functional copies of the alpha globin genes are present. Hb Bart syndrome is characterized by fetal onset generalized edema, severe anemia, hepatosplenomegaly, and usually death in the neonatal period. Complications, such as preeclampsia, premature delivery, and antepartum hemorrhage are common during pregnancy with a baby affected by Hb Bart syndrome. Blood transfusions, including in utero transfusions for Hb Bart syndrome, may be used as treatment for these disorders. The most common pathogenic variants causing alpha-thalassemia are large deletions of the HBA1 (NM_000558) and/or HBA2 (NM_000517) genes. Silent carriers and individuals with alpha-thalassemia trait are at risk of having a child with HbH syndrome. Additionally, individuals with alpha-thalassemia trait are at risk of having a child with Hb Bart syndrome if they have two functional copies of alpha globin on one chromosome and zero active copies of alpha globin on the other chromosome (--/%u03B1%u03B1). If one reproductive partner is a silent carrier and the other has alpha-thalassemia trait with a (--/%u03B1%u03B1) configuration, the risk for HbH in their children is 25%. When both reproductive partners have alpha-thalassemia trait, the risk for a child with HbH is 50% if one partner has a (--/%u03B1%u03B1) configuration and the risk for a child with Hb Bart syndrome is 25% if both partners have a (--/%u03B1%u03B1) configuration. Alpha thalassemia trait is common in Southeast Asian, African, West Indian, and Mediterranean populations with individuals of Southeast Asian descent more likely to have the (--/%u03B1%u03B1) configuration. This test can detect 0, 1, 2, 3, and 4 copies of HBA1 and HBA2 but the number of copies on each allele is not determined. Co-inheritance of abnormalities involving other hemoglobin genes may modify disease symptoms. Additionally, mutations in non-coding regulatory regions, which are not detected by this test, may also cause inactivation of alpha globin genes. This test is intended for pre/post-conception carrier screening and is not intended for diagnostic testing.