Sickle Cell Disease (SCD)


Sickle cell disease (SCD) comprises a group of inherited red blood cell disorders characterized by structural abnormalities of hemoglobin, the protein responsible for transporting oxygen in blood throughout the body.1 

In SCD, red blood cells containing abnormally structured hemoglobin are sickle-shaped and rigid, so that blood cannot flow through vessels. Circulatory obstruction may result in stroke, episodes of pain, infections, and eye problems.1 

Several different subtypes of SCD have been identified, including sickle cell anemia, sickle-hemoglobin C disease, sickle-hemoglobin D disease, sickle-hemoglobin E disease, sickle-hemoglobin O disease, sickle-beta zero thalassemia, and sickle-beta plus thalassemia.2 

Sickle Cell Anemia

Sickle cell anemia, also known as hemoglobin SS disease (HbSS), is the most common and most severe form of SCD. When a mutated beta globin gene (S) is inherited from each parent, the child produces only abnormal hemoglobin S.2 Sickle cell anemia affects predominantly persons of African and Indian heritage.3 

Sickle Cell Trait

People with sickle cell trait (SCT), also known as HbAS, inherit the sickle cell gene (S) from one parent and a normal gene (A) from the other parent. Such individuals are carriers of SCD and can pass the sickle cell gene along to their children. Individuals with SCT typically do not exhibit signs or symptoms of SCD; however, rarely, they may have health problems related to SCT. These include pain crises, problems on exposure to high atmospheric pressure (eg, scuba diving) or low oxygen levels (eg, high altitudes), and problems brought on by dehydration. 4,5

Sickle-Hemoglobin C Disease

This type of SCD, also known as HbSC, is usually relatively mild. The child inherits a sickle cell gene (hemoglobin S) from one parent and a gene for hemoglobin C from the other parent. A slightly different substitution within the beta globin gene results in an abnormal form of hemoglobin called hemoglobin C. Symptoms are milder in this form because blood cell counts are higher and anemia is less severe than in the HbSS type. The prevalence of this type of SCD is increased in individuals of West African, Middle Eastern, or Mediterranean heritage.3,4 

Sickle-Hemoglobin D Disease

Individuals with this type of SCD, also known as HbSD,  inherit a sickle cell gene (hemoglobin S) from one parent and from the other a mutant beta globin gene that produces an abnormal hemoglobin called hemoglobin D. This rare type of SCD is characterized by moderately severe anemia and infrequent pain episodes. The prevalence of this type of SCD is increased in individuals of Asian or Latin American heritage.3,4

Sickle-Hemoglobin E Disease

Individuals with this type of SCD, also known as HbSE, inherit a sickle cell gene (hemoglobin S) from one parent and from the other a mutant beta globin gene that produces an abnormal hemoglobin called hemoglobin E. This type of SCD is very rare, and severity is variable.4

Sickle-Hemoglobin O Disease

Individuals with this type of SCD, also known as HbSO, inherit a sickle cell gene (hemoglobin S) from one parent and from the other a mutant beta globin gene that produces an abnormal hemoglobin called hemoglobin O. This rare type of SCD affects primarily individuals of Arabian, North African, or Eastern Mediterranean heritage.3,4

Sickle-Beta Zero Thalassemia

Individuals with this type of SCD, also known as HbSB0, inherit a sickle cell gene (hemoglobin S) from one parent and a mutant gene for beta0 thalassemia from the other. Usually, people with this form of SCD have severe anemia, similar to what is seen in HbSS, because the only form of hemoglobin found in people with either HbSS or HbSB0 is hemoglobin S.2,4 

Sickle-Beta Plus Thalassemia

Individuals with this type of SCD, also known as HbSB+, inherit a sickle cell gene (hemoglobin S) from one parent and a mutant gene for beta+ thalassemia from the other.2,4  HbSB+ is usually milder than HbSS and HbSB0; however, the degree of severity is related to the amount of normal beta globin produced.2-4 Individuals with reduced amounts of normal beta globin have relatively mild symptoms, whereas individuals with no normal beta globin have severe symptoms, similar to those of HbSS, and require chronic blood transfusions.2,3 The prevalence of HbSB+ is increased among individuals of Mediterranean and Caribbean descent.3

References

  1. Sickle cell disease. NIH, National Heart Lung and Blood Institute. Accessed November 9, 2021.
  2. Types of sickle cell. Global Blood Therapeutics. Accessed November 9, 2021.
  3. Types of sickle cell disease. Sickle Cell Association of the National Capital Area, Inc. Accessed November 9, 2021.
  4. What is sickle cell disease? Centers for Disease Control and Prevention. Reviewed December 14, 2020. Accessed November 9, 2021.
  5. What is sickle cell trait? Centers for Disease Control and Prevention. Reviewed December 14, 2020. Accessed November 9, 2021. 

Reviewed by Harshi Dhingra, MD, on 11/9/2021.

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