Sickle Cell Genetics and Types of Sickle Cell Disease
Sickle cell disease results from the inheritance of two abnormal hemoglobin genes. Individuals who possess only one copy of the sickle cell mutation have what is known as sickle cell trait, which typically does not lead to any significant health issues. It is worth noting that many individuals may be unaware that they carry the sickle cell mutation. When two individuals with sickle cell trait have children together, there is a possibility that their offspring may be born with sickle cell disease.
Types of Sickle Cell Disease
Hemoglobin SS
Two-thirds of people with sickle cell disease have hemoglobin SS disease, which occurs when two copies of the abnormal hemoglobin S mutation are inherited, one from each parent. Hemoglobin SS disease is sometimes referred to as sickle cell anemia and is considered the most severe form of sickle cell disease. There is significant variability from one patient to another for all types of sickle cell disease.
Hemoglobin SC
The second most common type of sickle cell disease is hemoglobin SC, which occurs when one copy of the hemoglobin S gene is inherited from one parent and one copy of hemoglobin C is inherited from the other parent. In this case, one parent has sickle cell trait and the other parent has hemoglobin C trait. Hemoglobin represents approximately 20% of the sickle cell disease in the U.S. Hemoglobin SC is typically less severe than hemoglobin SS, particularly during childhood, but can develop into a severe condition for some individuals as they grow older.
Hemoglobin S/Beta-Thalassemia
There are hundreds of mutations that can occur in the hemoglobin gene that are referred to as beta-thalassemia mutations. Some of these mutations are very severe, called beta-0 mutations, resulting in no production of normal hemoglobin. Others, less severe beta-plus mutations, reduce the amount, or affect the function, of hemoglobin produced. Hemoglobin S/Beta-thalassemia occurs when one copy of hemoglobin S is inherited with one of these abnormal beta-thalassemia mutations. When that mutation is severe (beta-0), this is called hemoglobin S/beta-zero-thalassemia. It is much the same as hemoglobin SS disease. Hemoglobin S/Beta-plus thalassemia is typically less severe but there is great variability depending on the type of beta-thalassemia mutation.
Other Types of Sickle Cell Disease
There are a number of other, less common types of sickle cell disease that occur when hemoglobin S is inherited from one parent and another rare hemoglobin is inherited from the other parent. The clinical severity of these rare types of sickle cell disease is highly variable.