Sickle cell disease (SCD) describes a group of genetic blood disorders. According to the Centers for Disease Control and Prevention (CDC) around 100,000 Americans have SCD. The CDC further explains that those with SCD are primarily of African descent but that SCD also affects those from South America, Central America, the Caribbean, and the Mediterranean.
The National Institute of Health (NIH) explains that SCD affects red blood cells by affecting hemoglobin, the protein in red blood cells that transports oxygen through the body. The hemoglobin protein is comprised of four protein subunits, two of which are called beta-globin and are produced by the HBB gene. Each person has two HBB genes, one inherited from each parent. Some mutations in the HBB gene produce an abnormal beta-globin that functions improperly. For people who develop SCD, both HBB genes are thus mutated and at least one produces an abnormal beta-globin called hemoglobin S (HbS). The second HBB mutation also produces an abnormal beta-globin, either HbS or another variant like hemoglobin C (HbC), D (HbD), E (HbE), O (HbO), or β (Hbβ). This variable second mutation defines the distinction between various forms of SCD. The most severe form of SCD, sickle cell anemia (HbSS), occurs when individuals inherit copies of the HbS gene from both parents, and thus are only able to produce hemoglobin S.
According to the National Heart, Lung, and Blood Institute of the NIH, inheriting mutated hemoglobin genes alters the functional capacity of red blood cells. Red blood cells with normal hemoglobin are round, giving them a flexibility that allows them to circulate through blood vessels of all sizes and transport oxygen throughout the body. Abnormal hemoglobin can stick together to form long rods that cause red blood cell to be sickle shaped and inflexible. This inflexibility has two primary consequences:
- Less blood flow: Blood cells are more easily caught on the sides of blood vessels, either slowing the flow of blood or stopping it entirely. The lack of red blood cells in parts of the body can cause:
- Acute and chronic pain;
- Delayed growth; and
- Organ complications, particularly in the liver, kidney, heart, and eyes.
- Anemia: Blood cells have a shorter life span because they burst easily. The lifespan of sickle cells is 10 to 20 days instead of the normal 90 to 120 days, making it difficult for the body to produce enough blood cells to keep up with blood cell turnover rate.
- Other complications include increased infections, liver failure, brain development problems, kidney problems, heart disease, priapism, gallstones, ulcers, delayed puberty, and pregnancy problems.
Mutations in HBB are the primary cause of SCD. However, as evidenced by the diversity in symptoms between people with the same mutations, other genetic factors are likely to play a less direct role as modifiers of the disease. Many of these genetic factors are unknown or modify SCD through unknown pathways. Identifying and understanding the heritable genetic factors that affect expression of SCD could lead to improvements in treatments and general health care.