This test is designed to detect carriers of sickle cell anemia and beta thalassemia. Sickle cell disease is an autosomal recessive blood disorder caused by misshapen red blood cells which result in deficiency of functional red blood cells and blockages of blood flow. Symptoms of sickle cell disease include severe anemia, swelling of the hands and feet, splenic enlargement and infarction, increased risk of infection, acute pain crises, and multisystem organ damage. Life expectancy is shortened and infection, acute chest syndrome, pulmonary hypertension, and cerebrovascular events are the primary causes of death. Sickle cell disease (MIM 603903) is caused by a pathogenic variant in the HBB gene (NM_000518) known as HbS (p.Glu7Val). Affected individuals are either homozygous for HbS or compound heterozygous with HbS on one allele and another pathogenic HBB variant, in some cases a beta thalassemia variant, on the second allele. Sickle cell trait refers to individuals who are heterozygous HbS carriers and are at risk of having a child with sickle cell disease. If both reproductive partners are HbS carriers or if one is an HbS carrier and the other is a carrier of another pathogenic HBB variant, the risk for sickle cell disease in their children is 25%. HbS carriers are usually asymptomatic, but may be at risk for vaso-occulsive events, splenic infarct, and kidney cancer. Sickle cell disease has a high incidence in African populations (approximately 1 in 400 individuals), and is also common in individuals of Mediterranean, Middle Eastern, and Indian descent. Co-inheritance of abnormalities involving other hemoglobin genes may modify disease symptoms.
Beta thalassemia is an autosomal recessive blood disorder that results from deficiency of functional hemoglobin typically due to decrease in the production of beta globin chains. Beta thalassemia major usually presents in the first two years of life and is characterized by severe anemia, hepatosplenomegaly, and, if untreated, failure to thrive with death before the age of 20. Regular blood transfusions with chelation therapy improve the prognosis. Beta thalassemia intermedia is a less severe disorder with later onset. Individuals with beta thalassemia intermedia have milder symptoms and generally do not require regular blood transfusions. Beta thalassemia (MIM 613985) is caused by pathogenic variants in the HBB gene (NM_000518). Beta thalassemia minor refers to individuals who are carriers of a heterozygous pathogenic HBB thalassemia variant and are at risk of having a child with beta thalassemia. If both reproductive partners are beta thalassemia carriers, the risk for beta thalassemia in their children is 25%. Beta thalassemia carriers are usually asymptomatic but some may have mild anemia. Beta-thalassemia is more common in individuals of Mediterranean, Asian, Middle Eastern, Hispanic, and West Indian descent. Co-inheritance of abnormalities involving other hemoglobin genes may modify disease symptoms. Additionally, beta thalassemia carriers have a 25% chance of having a child with sickle cell disease, if their reproductive partner has sickle cell trait. This test is intended for pre/post-conception carrier screening and is not intended for diagnostic testing.