Beta-Globin-Related Hemoglobinopathies (HBB)
Pathogenic variants in the beta-globin gene (HBB) cause a variety of autosomal recessive diseases of aberrant hemoglobin, the protein that carries oxygen in the blood. The most frequent hemoglobinopathies are beta-thalassemia, sickle cell disease and HbC disease. In individuals with beta-thalassemia, hemoglobin is not properly synthesized and results in small red blood cells that are inefficient at carrying oxygen. Individuals with severe beta-thalassemia require life-long blood transfusions and chelation therapy to remove the extra iron that results from the blood transfusions. Individuals with milder forms of beta-thalassemia may not require transfusions. Although current treatments can extend the life expectancy into adulthood, patients usually do not survive beyond their 30s as a result of cardiac complications of iron overload. Sickle cell disease is caused by the inheritance of two copies of Hemoglobin S (HbS), encoded by a specific HBB variant. Symptoms typically first present in infancy or childhood and include chronic anemia, pain and/or swelling in the hands and feet, episodes of severe pain, and infections. The clinical presentation is highly variable between affected individuals. The life expectancy for individuals with sickle cell disease is in the 40s but may be increasing. HbS can also cause related diseases if it is inherited along with a different type of variant in HBB. HbC disease is caused by the inheritance of two copies of Hemoglobin C (HbC), encoded by a specific HBB variant. HbC disease causes mild anemia in some patients, but the majority of affected individuals do not have any symptoms and have a normal life expectancy. HbC can also cause disease if it is inherited with another type of abnormal hemoglobin, the most common being HbS. The inheritance of one copy each of HbS and HbC result in SC disease, which may cause chronic anemia, pain and/or swelling in the hands and feet, episodes of severe pain, infections, and retinal disease. The life expectancy for individuals with SC disease is in the 60s. The type of disease that will develop can be predicted based on the variants inherited. Variants causing beta-thalassemia are prevalent in Mediterranean and South-East Asian populations, whereas HbS is most common in people of African, Mediterranean, Middle Eastern, and Indian ancestry. HbC is most common in people of African descent.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.