Genetic: Sickle Cell Anemia

Definition
Description
Demographics
Causes and Symptoms
Diagnosis
Treatment
Prognosis
Prevention
The Future
For more information

Definition

Sickle cell anemia is an inherited blood disorder caused by a mutation in a gene responsible for the production of hemoglobin, the protein found in red blood cells that carries oxygen from the lungs to other body organs and tissues. The disorder was first described in 1910 by James Herrick (1861–1954), a doctor in Chicago who was examining a young black dental student from the West Indies. Herrick described the cells seen in a smear of the patient's blood under the microscope as “thin,

sickle-shaped and crescent-shaped red cells.” The dental student died in 1916 at the young age of thirty-two.

A person must inherit the defective gene that produces hemoglobin S from both parents in order to develop sickle cell anemia. A person who inherits the gene from only one parent is said to have sickle cell trait. People with sickle cell trait do not have the symptoms of the disease but can pass on the disease if they have children with another carrier.

Description

In sickle cell anemia, the red blood cells do not contain normal hemoglobin but a defective form of the protein called hemoglobin S. Whereas normal red blood cells are round, flexible, and able to move easily through the blood vessels, cells containing hemoglobin S can bend into crescent or sickle shapes and become sticky. They cause health problems for two reasons. First, blood cells containing hemoglobin S die much faster than normal red blood cells; this lowers their ability to carry enough oxygen to meet the body's needs and leads to such symptoms as lack of energy and lightheadedness or dizziness. Second, the abnormal red blood cells tend to form clumps that block blood vessels and cause organ damage.

When the sickle cells block blood vessels, they cause such symptoms as chest pain, damage to the spleen, liver, and kidneys, and stroke. Two-thirds of all strokes in people with sickle cell anemia occur in children, with an average age of eight years. Another common complication is sickle cell crisis, a sudden severe attack of pain that affects the patient's chest, joints, abdomen, bones, or extremities.

Damage to the spleen caused by the abnormal blood cells makes patients with sickle cell anemia vulnerable to certain infections. Last, the effects of the sickle cells on the narrow blood vessels in the eyes lead to vision problems that include disorders of the retina and bleeding into the eye.

Demographics

Geneticists think that the defective gene responsible for hemoglobin S originated independently in five different parts of Africa, including Cameroon and Senegal, and Saudi Arabia. The gene did not die out because, even though people with two copies of the defective gene did not usually live long enough to have children, those who had only the sickle cell trait were more resistant to one type of malaria. This advantage helped them to survive in parts of the world where malaria is

widespread. Sickle cell anemia is still more common in Africa, India, parts of Central and South America, the Caribbean islands, Saudi Arabia, and Turkey than in Europe or North America.

In the United States, sickle cell anemia primarily affects African Americans. About 80,000 people in the United States presently have sickle cell disease, which makes it the most common inherited blood disorder in North America. It occurs in one in every 375 live births among African Americans. According to the National Institutes of Health (NIH); 2 million Americans have sickle cell trait—one in twelve African Americans and one in every 100 Hispanics.

Males and females are equally likely to inherit either the trait or the disease.

Causes and Symptoms

Sickle cell anemia is caused by a mutation in the hemoglobin-beta gene on chromosome 11.

The symptoms of sickle cell anemia do not usually appear in infants until they are about four months old. Severity differs from patient to patient.

• Anemia. Symptoms of sickle cell disease related to anemia include fatigue, pale skin, dizziness or feeling faint, cold hands or feet, and shortness of breath.

• Sickle cell crises. These are episodes of severe pain caused by defective red blood cells blocking the flow of blood through the blood vessels that supply the chest, joints, bones, or abdomen. Crises occur suddenly and may last for anywhere from a few hours to several weeks. Some people have only a few crises during their lifetime while others may have a dozen or more every year.
• Vulnerability to infection. People with sickle cell anemia are more likely to get frequent infections because of damage to the spleen caused by the disease. Pneumonia, a lung infection, is the most common cause of death in children with sickle cell anemia.
• Jaundice. Jaundice is a condition in which the whites of the eyes and the skin have a yellowish discoloration because of liver problems.
• Hand/foot syndrome. This is often the first symptom of sickle cell anemia in babies. The child's hands and feet become swollen because the defective blood cells block the veins in the hands and feet and do not allow blood to return freely to the circulation.
• Eye disorders. Defective red blood cells blocking the tiny blood vessels in the eyes can damage the retina, the light-sensitive layer of tissue at the back of the eyeball.
• Stunted growth and delayed puberty.
• Stroke. Although stroke is unusual in most children, about 11 percent of children with sickle cell disease suffer a stroke before they are twenty years old. Convulsions and partial paralysis often accompany stroke in this age group.

A Great Jazz Musician

Miles Davis (1926–1991) was a jazz trumpeter and composer who was considered one of the most influential American musicians of the twentieth century. Davis helped to shape most of the major developments in jazz from the World War II period through his death in 1991. The son of a dentist in Alton, Illinois, Davis started to play the trumpet at age thirteen. He won a scholarship to the prestigious Julliard School of Music in New York in 1944, but quit to make his first professional recordings in 1945.

Davis was fortunate in suffering from a relatively mild form of sickle cell disease. He did, however, make his condition worse by becoming addicted to heroin and other drugs during his first visit to Paris in 1949. He had to take frequent breaks from his career in the 1960s and 1970s because of the impact of his drug abuse on the health of his bones, already weakened by sickle cell anemia. Davis eventually had to have a hip replacement in 1976. His death at the age of sixty-five was caused by a stroke combined with pneumonia, both complications of a sickle cell crisis.

Diagnosis

As of 2008, forty-nine states in the United States routinely screened newborns for sickle cell anemia through a blood test. A small amount of

blood from the baby's finger or heel and sends is sent to a laboratory where it is analyzed for hemoglobin S. Older children and adults can also be tested for hemoglobin S with a blood test.

If the screening test is negative, no further testing is required. If the test results are positive for hemoglobin S, a second test is done to determine whether the person has sickle cell trait or the disease itself.

Treatment

Treatment depends on the type and severity of the patient's symptoms. The only cure for sickle cell anemia is a bone marrow transplant (BMT). Only about 18 percent of children with the disease, however, have a suitable donor—usually a full sibling. The transplant procedure itself is complex, and 6 percent of children die during the procedure. As of 2008, BMT was usually performed only on children with a high risk of stroke, major risk of bleeding in the brain, severe visual disorders, and more than two sickle cell crises per year for several years.

Medications are the mainstay of treatment for patients with sickle cell anemia:

• Pain relievers. Depending on the severity of pain, patients with sickle cell anemia may be given prescription pain relievers during a sickle cell crisis. In some cases they may be taken to the hospital for intravenous fluids and strong narcotic painkillers.
• Antibiotics. Children diagnosed with sickle cell anemia are usually given penicillin from two months to five years of age to prevent infections. Adults with the disease may also be given antibiotics if they develop a bacterial infection.
• Hydroxyurea. Hydroxyurea is a drug developed to treat cancer that helps some people with sickle cell disease. It stimulates the production of fetal hemoglobin, a type of hemoglobin usually found only in newborns. It can reduce the need for blood transfusions and the frequency of sickle cell crises.
• Supplemental oxygen. Patients who are hospitalized with a severe crisis may be given supplemental oxygen to breathe to help raise the levels of oxygen in their blood and body tissues.

Blood transfusions lower the risk of stroke and relieve anemia in children with sickle cell anemia. Healthy red blood cells are removed from donated blood and infused into the veins of sickle cell patients. The risk

of blood transfusions, however, is the buildup of iron in the patient's body, which can damage the liver and other organs. The Food and Drug Administration approved the drug Exjade in 2005, which removes excess iron from the blood.

Some lifestyle adjustments can help to lower the risk of sickle cell crises. Fevers, exposure to cold weather, becoming dehydrated, and using recreational drugs and alcohol have been found to trigger crises. Avoiding exposure to infections, drinking plenty of fluids, lowering emotional stress levels, and avoiding drugs and alcohol are all recommended for those with sickle cell anemia.

Prognosis

The prognosis for sickle cell anemia is still relatively poor. With the exception of children who benefit from bone marrow transplantation, most people with sickle cell anemia have shortened life expectancies. As recently as the 1990s, the average life span for patients with the disease was forty-two years for males and forty-eight years for females. As of 2008, about half of patients diagnosed with the disease lived into their early fifties.

Prevention

The only way to prevent sickle cell disease is genetic counseling and testing. People can be tested for the sickle cell trait before starting a family and can talk to a counselor about their risk of having a child with sickle cell disease. It is also possible to test an unborn baby for sickle cell disease by a procedure called amniocentesis. The doctor uses a needle to withdraw a small sample of the fluid surrounding the baby in the mother's uterus. The cells in the sample are then tested for the defective hemoglobin S gene.

The Future

There were several potential treatments for sickle cell anemia under investigation as of 2008. One is gene therapy. Experiments done in mice in the early 2000s have encouraged some researchers to think that it might be possible to remove some of the bone marrow cells in patients with sickle cell anemia, replace the defective hemoglobin-beta gene with a normal gene, and return the “corrected” cells to the patient's bone marrow.

Other treatments that are considered experimental are clotrimazole, an antifungal medication that appears to slow the production of sickle cells; and nitric oxide, a gas that helps to keep blood vessels open and reduce the stickiness of sickle cells.

SEE ALSO Malaria; Stroke; Thalassemia

WORDS TO KNOW

Anemia: A condition in which a person's blood does not have enough volume, enough red blood cells, or enough hemoglobin in the cells to keep body tissues supplied with oxygen.

Hemoglobin: An iron-containing protein in red blood cells that carries oxygen from the lungs to the rest of the body.

Sickle cell crisis: Sudden onset of pain and organ damage in the chest, bones, abdomen, or joints caused by defective red blood cells blocking blood vessels.

For more information

BOOKS

Jones, Phill. Sickle Cell Disease. New York: Chelsea House, 2008.

Peak, Lizabeth. Sickle Cell Disease. Detroit, MI: Lucent Books, 2008.

Peterson, Judy Monroe. Sickle Cell Anemia. New York: Rosen Publishing Group, 2009.

WEB SITES

Dolan DNA Learning Center. Sickle Cell Disease. Available online at http://www.ygyh.org/sickle/whatisit.htm (accessed August 22, 2008). This is an interactive multimedia site about sickle cell anemia.

Mayo Clinic. Sickle Cell Anemia. Available online at http://www.mayoclinic.com/health/sickle-cell-anemia/DS00324 (updated March 28, 2007; accessed August 22, 2008).

National Heart, Lung, and Blood Institute (NHLBI).What Is Sickle Cell Anemia? Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html (updated August 2008; accessed August 22, 2008). National Human Genome Research Institute (NHGRI). Learning about Sickle

Cell Disease. Available online at http://www.genome.gov/10001219 (updated May 30, 2008; accessed August 22, 2008). Sickle Cell Disease Association of America (SCDAA). About Sickle Cell Disease.

Available online at http://www.sicklecelldisease.org/about_scd/index.phtml (accessed August 22, 2008).