What are the signs and symptoms?
Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain. The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.
The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice. Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.
How common is sickle cell disease?
Sickle cell disease affects millions of people worldwide. It is most common among people whose ancestors come from Africa; Mediterranean countries such as Greece, Turkey, and Italy; the Arabian Peninsula; India; and Spanish-speaking regions in South America, Central America, and parts of the Caribbean.
Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.
What genes are related to sickle cell disease?
Mutations in the hemoglobin, beta gene (HBB) cause sickle cell disease. Hemoglobin consists of four protein subunits, typically, two subunits called alpha hemoglobin and two subunits called beta hemoglobin. The HBB gene provides instructions for making beta hemoglobin. Various versions of beta hemoglobin result from different mutations in the HBB gene. One particular HBB mutation produces an abnormal version of beta hemoglobin known as hemoglobin S (HbS). Other mutations in the HBB gene lead to additional abnormal versions of beta hemoglobin such as hemoglobin C (HbC) and hemoglobin E (HbE). HBB mutations can also result in an unusually low level of beta-hemoglobin; this abnormality is called beta thalassemia.
In people with sickle cell disease, at least one of the beta hemoglobin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta hemoglobin subunits in hemoglobin. In other types of sickle cell disease, just one beta hemoglobin subunit in hemoglobin is replaced with hemoglobin S. The other beta hemoglobin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta hemoglobin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia (HbSBetaThal) disease.
Abnormal versions of beta hemoglobin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.
Read more about the HBB gene.
How do people inherit sickle cell disease?