Understanding Sickle Cell Disease
Sickle cell disease (SCD) is a group of inherited red blood cell disorders affecting millions worldwide. Learn about its causes, types, and impact.
What is Sickle Cell Disease?
Sickle cell disease is a group of inherited red blood cell disorders. In someone who has SCD, the red blood cells become hard and sticky and look like a C-shaped farm tool called a "sickle." These cells can block blood flow, causing pain and other serious problems such as infection, acute chest syndrome, and stroke.
Normal red blood cells are round and move easily through blood vessels to carry oxygen throughout the body. In sickle cell disease, the red blood cells become rigid and sticky, causing them to get stuck in small blood vessels and block the flow of blood and oxygen to organs in the body.
Types of Sickle Cell Disease
People with this form inherit two sickle cell genes ("S"), one from each parent. This is often called sickle cell anemia and is usually the most severe form of the disease.
People with this form inherit one sickle cell gene ("S") from one parent and one gene for an abnormal hemoglobin called "C" from the other parent. This is usually a milder form of SCD.
People with this form inherit one sickle cell gene ("S") from one parent and one gene for beta thalassemia from the other parent. Symptoms are generally less severe than HbSS.
This is usually a severe form of SCD. People with this form inherit one sickle cell gene ("S") and one gene for beta-zero thalassemia, which is a severe type of beta thalassemia.
There are also rarer forms of SCD, such as Hemoglobin SD, Hemoglobin SE, and Hemoglobin SO, which occur when the hemoglobin S gene is paired with another abnormal hemoglobin gene.
History and Discovery
Sickle cell disease was first described in 1910 when Dr. James B. Herrick observed "peculiar elongated and sickle-shaped" red blood cells in a patient. His intern, Ernest Irons, first identified these abnormal cells in the blood of Walter Clement Noel, a dental student from Grenada who was admitted to the Chicago Presbyterian Hospital suffering from anemia.
In 1949, Dr. Linus Pauling and colleagues demonstrated that SCD was caused by an abnormal protein in the hemoglobin. This was the first disease proven to be the result of a specific molecular alteration of a protein, making it a landmark in molecular medicine.
In 1956, Vernon Ingram discovered the specific molecular defect in hemoglobin that causes sickle cell disease: a single amino acid substitution in the beta-globin chain of hemoglobin. This discovery marked the beginning of molecular medicine.
Pathophysiology
The fundamental problem in sickle cell disease is the production of abnormal hemoglobin S (HbS). When this hemoglobin gives up its oxygen to the tissues, it can form rigid polymers (long chains) within the red blood cell, causing the cell to become rigid and take on the characteristic sickle shape.
These sickled cells can:
- Block small blood vessels, causing pain and organ damage
- Break down prematurely, leading to anemia
- Cause the spleen to enlarge and eventually stop functioning properly, increasing the risk of serious infections
- Lead to chronic inflammation and damage to blood vessels
The severity of symptoms varies widely among individuals with sickle cell disease, depending on the specific genetic mutation, environmental factors, and other genetic modifiers.