Table of Contents
Definition of Sickle Cell Disease
An inherited genetic disorder of defective hemoglobin, a protein compound erythrocytes (red blood cells) contain that binds with oxygen. Though the primary effect of sickle cell disease, also called sickle cell anemia, is anemia (insufficient oxygen in the blood), the condition also causes significant pain and damage to organs throughout the body.
In the United States sickle cell disease is significantly more common in African Americans. Around the world, sickle cell disease is most common among people of African, northern Mediterranean, Indian, and Middle Eastern descent.
About 70,000 Americans have sickle cell disease and another 2 million have sickle cell trait. Sickle cell disease is the most common inherited blood disorder.
Sickle cell disease gets its name from the characteristic sickle shape of the erythrocytes. The deformity results from the defective hemoglobin, called hemoglobin S, which the erythrocytes carry. When hemoglobin S releases oxygen during the oxygen-carbon dioxide exchange, it polymerizes its structure undergoes molecular changes that cause its molecular weight to increase. This stiffens and hardens the normally flexible erythrocytes, pulling them into a sickle or crescent shape.
The rigidity and inflexibility prevents the erythrocytes from folding and twisting as they pass through the small blood vessels, causing them to create blockages. The blockages cause swelling, pain, and eventually damage to organs and structures throughout the body. People who have sickle cell disease have very high risk for stroke, heart attack, acute chest syndrome (blockages in the lungs that cause infection), and loss of vision.
The changes also make the erythrocytes more fragile, and they easily break apart as the flow of blood jostles them around. Sickled erythrocytes die after only about 20 days in the blood circulation, whereas normal erythrocytes live for 90 to 120 days. The shortened lifespan further limits the ability of the blood to transport oxygen, establishing chronic anemia.
Researchers believe the gene mutation that causes sickle cell disease originated in the form of sickle cell trait as an adaptation to protect against malaria infection. The sickled erythrocytes resist the parasite that causes malaria. In sickle cell trait, the person has some hemoglobin S and mostly normal hemoglobin-an ideal blend for simultaneously maintaining health and thwarting malaria. The adaptation backfires only when two people with sickle cell trait conceive a child, at which time the recessive autosomal inheritance pattern of the mutated hemoglobin gene becomes a risk for passing on too much of a good thing to the child.
The inheritance pattern for sickle cell disease is autosomal recessive, which means both parents must pass the defective hemoglobin gene to their child. People who are carriers of the mutated hemoglobin gene have sickle cell trait, with one mutated and one normal hemoglobin gene. They have small amounts of hemoglobin S though mostly have normal hemoglobin and have no indications of sickle cell disease. However, their children may end up with sickle cell disease if they inherit the sickle cell mutation from each parent.
When both parents have sickle cell trait, there is a 1 in 4 chance for the child to have sickle cell disease, a 2 in 4 chance the child will also be a carrier, and a 1 in 4 chance the child will inherit two normal genes.
Symptoms of Sickle Cell Disease and Diagnostic Path
Symptoms generally begin to emerge when a child is about a year old. For the first year of life the child has an abundant supply of fetal hemoglobin, which has the ability to prevent polymerization of hemoglobin S. However, the child’s own hemoglobin gradually replaces the fetal hemoglobin and this protection disappears, typically between age 6 months and 10 months.
Early symptoms of sickle cell disease in a child are swollen hands and feet (sometimes called hand and foot syndrome), a consequence of damaged erythrocytes blocking the small blood vessels in the hands and feet to prevent blood from circulating out. Other symptoms include
People who have sickle cell disease may also have
- Frequent infections resulting from damage to the spleen and lymph tissues
- Jaundice, yellow discoloration of the skin resulting from excessive bilirubin in the blood circulation as the components of the dead erythrocytes accumulate in the liver
- Delayed growth due to severe anemia
A blood test can detect the presence of hemoglobin S, which affirms the diagnosis. In the United States, hospitals routinely run this test on all newborns. Examination of the erythrocytes under the microscope also shows the characteristic sickle shape.
Sickle Cell Disease Treatment Options and Outlook
Treatment for sickle cell disease may include analgesic medications for pain relief, blood transfusions to replace the damaged erythrocytes with healthy erythrocytes (which is effective for the life cycle of the transfused erythrocytes), and the medication hydroxurea (which can reestablish fetal hemoglobin production in some children).
Bone marrow transplantation is sometimes an option for people who have severe symptoms. There is no cure for sickle cell disease. Sickle cell trait does not produce symptoms or develop into sickle cell disease, so it requires no treatment. Many people who have sickle cell trait do not know it.
Risk Factors and Preventive Measures
Because sickle cell disease is an inherited genetic disorder, the only risk factor is heredity. It is a good idea for people who do not know their sickle cell status, especially African Americans, to have the blood test for hemoglobin S before conceiving children. Genetic counseling can help with family planning decisions when both parents have sickle cell trait.