Genetic Variation Leading to Sickle Cell Anemia: Insights into the Underlying Mutation
Sickle cell anemia is a severe form of sickle cell disease (SCD), a condition that affects the production of hemoglobin, a protein within red blood cells that carries oxygen. This type of SCD is most commonly encountered, and it arises when a person inherits a hemoglobin-Beta gene with a mutation from both biological parents, coding for hemoglobin-S instead of the usual hemoglobin-A.
People living with SCD face numerous health challenges, including chronic anemia, recurrent episodes of severe pain known as sickle cell crises, acute chest syndrome, stroke, organ damage, infections, bone and joint problems, and more.
Chronic anemia causes symptoms such as fatigue, pale skin, and shortness of breath due to the rapid breakdown of abnormal sickle-shaped red blood cells. Pain crises are characterized by intense episodes of pain in various parts of the body, such as the abdomen, chest, back, arms, or legs, caused by blocked blood flow. Acute chest syndrome, a potentially life-threatening complication, presents with chest pain, cough, fever, and difficulty breathing. Stroke or silent neurological damage can lead to weakness, vision loss, seizures, or cognitive impairments. Avascular necrosis, or bone tissue death, results in chronic bone and joint pain and disability. Organ damage to the spleen, kidneys, liver, and heart can lead to swelling, reduced function, and increased infection risk. Infections, especially in infants and young children, are common due to spleen damage impairing the immune defense. Other complications include leg ulcers, gallstones, retinopathy, hearing loss, and priapism (painful prolonged erections in males).
Sickle cell anemia predominantly affects African Americans, with about 1 in 365 African American babies born with the disease and roughly 1 in 13 carrying the trait. Hispanic Americans also have a smaller, but notable incidence (approximately 1 in 16,300 births). The disease disproportionately burdens Black populations due to both genetic prevalence and social determinants affecting healthcare access and management. Complications appear across ethnic groups but are principally observed in those of African descent and, to a lesser extent, Hispanic and some Mediterranean or Middle Eastern populations. Variants such as HbSC disease show somewhat different patterns of complications, including higher rates of splenomegaly and retinopathy compared to classic sickle cell anemia (HbSS).
If both biological parents carry the HBB gene with the mutation that produces hemoglobin-S, there is a risk that each child they have will be born with sickle cell anemia. If a person inherits one HBB gene with the mutation that produces hemoglobin-S and one typical HBB gene that produces hemoglobin-A, there is a 50% risk that they will carry the sickle cell trait (SCT).
Management of SCD requires careful, lifelong medical care due to the diverse and severe complications linked to the disease. In the United States, approximately 100,000 people have SCD, and most of them receive Medicaid. However, less than 70% of doctors in the U.S. accept new Medicaid beneficiaries, posing a challenge for many patients.
Individuals with SCD should call 911 immediately if they experience severe headache, fever, sudden weakness or numbness, chest pain, seizures, difficulty breathing, swelling in the abdomen, painful erection of the penis that lasts more than 4 hours, or sudden vision issues. They should also speak with a doctor for advice about how to manage their SCD. If red blood cells containing hemoglobin-S build up and cause blockages in the blood vessels, they can lead to pain and serious health complications.
In summary, sickle cell anemia causes widespread systemic complications affecting blood flow and organ function, with the highest prevalence and impact among African-descended populations. It is crucial for individuals with SCD to receive prompt and appropriate medical care, and for healthcare providers to be aware of the unique challenges faced by this patient population.
