Sickle cell disease is a group of inherited disorders. The specific type of SCD a person has depends on which HBB gene mutations they inherited from their parents. The HBB gene gives instructions for a part of hemoglobin, which is the protein that travels through the blood to deliver oxygen throughout the body.1
People with all types of SCD inherit the gene for hemoglobin S from 1 parent and a gene for another type of hemoglobin from 1 parent. Hemoglobin S (also called sickle hemoglobin) is the most common type of abnormal hemoglobin. It has a mutation that causes it to form rigid strands that make red blood cells stiff and sickle-shaped.1
Some types of SCD may show more severe symptoms. However, severity also varies within each type because of other genetic and environmental factors. A simple blood test can determine what type of SCD you have.
Sickle cell anemia (HbSS)
Sickle cell anemia is the most common and severe type of SCD. It happens when a person inherits 2 genes for hemoglobin S (1 from each parent). Hemoglobin S clumps together inside red blood cells. This makes red blood cells rigid and sickle-shaped. Sickle cells can block blood flow and break apart too soon.2
This causes people with sickle cell anemia to experience chronic anemia (lack of red blood cells), unpredictable episodes of pain, and widespread organ damage. The severity and life expectancy of sickle cell anemia varies, but it is improving with better screening and treatments.3
Sickle cell trait (HbAS)
When someone inherits 1 gene for hemoglobin S and 1 gene for normal hemoglobin A, they have sickle cell trait. They usually do not have any signs of the disease and live a normal life. However, they can pass on the hemoglobin S gene to their children.4
People with sickle cell trait have enough normal hemoglobin to prevent red blood cells from sickling. This means they will usually not experience any complications. In rare cases, people with sickle cell trait may experience pain crises. These may be worsened by low oxygen levels in the air, dehydration, or high altitudes.4
HbSC
People with this type of SCD inherit a gene for hemoglobin S and a gene for an abnormal hemoglobin called hemoglobin C. Hemoglobin C also has a mutation that changes the shape of red blood cells. The gene for hemoglobin C is most common in individuals with West African ancestry.3
People with HbSC usually experience milder anemia and less frequent complications than people with sickle cell anemia. One complication of HbSC occurs when blood vessels form around the eyes to make up for a lack of oxygen there. This is called proliferative sickle cell retinopathy, and it can lead to vision loss.5
Another complication of HbSC results from reduced blood flow to bones in joints. This can cause a painful condition known as osteonecrosis, where bone breaks down faster than the body can replace it.5
HbS beta-thalassemia
People with HbS beta-thalassemia inherit a gene for hemoglobin S from 1 parent and a gene for beta-thalassemia from the other parent. Beta-thalassemia is a disease that results in reduced production of hemoglobin. Depending on the mutation, people may have no normal hemoglobin (HbS beta zero thalassemia) or a low amount of normal hemoglobin (HbS beta plus thalassemia).6
People with HbS beta zero thalassemia show similar complications as people with sickle cell anemia. People with HbS beta plus thalassemia usually show milder symptoms. Severe and moderate forms are most common in the eastern Mediterranean region and parts of India. Milder forms are common in populations of African ancestry.3
Other types of sickle cell disease
Less common types of SCD include HbSD, HbSE, and HbSO. These happen when someone inherits 1 gene for hemoglobin S from 1 parent and a gene for another abnormal hemoglobin (D, E, or O) from the other parent.2
People with HbSD have moderate anemia and occasional pain episodes. It is most common in people with Asian and Latin American ancestry. People with HbSE experience some symptoms of sickle cell anemia, including moderate anemia and increased risk of infection. It is most common among people of South and Southeast Asian descent. People with HbSO usually have symptoms of sickle cell anemia. It is most common in people of Arabian, North African, and Eastern Mediterranean descent.7–9
