Sickle-Cell Anemia

Sickle-cell anemia (Hb S) is an inherited autosomal (“non-sex” chromosomes) recessive blood disease that affects millions of people throughout the world. It is caused by a mutation in the gene for beta hemoglobin (an oxygen-carrying molecule), producing a change in the shape of the red blood cell into a sickle shape. The distorted shape of the red blood cell is unable to pass through capillaries and causes blood clots to form. Consequently, these blockages impede the flow of blood, causing hemorrhaging as red blood cells (RBCs) enter surrounding tissue, giving rise to many complications throughout the body.

The disease was first discovered in Chicago in 1910 by James B. Herrick, who described the anemia as “peculiar elongated sickle-shaped” red blood cells in a young black student from the West Indies. Many scholars acknowledge that even before Herrick, the awareness of African cultures with the disease was characterized by the intense and chronic pain of the disease. This explains the early name “Chwechweechwe” given to the disease, which was a description of the recurring pain experienced by the patient.

Physical anthropologists of antiquity used “racial admixture” and “Negro blood” to imply that there was an inherent difference between the black and white races. However, with time, as physicians continued to discover sickle-shaped cells in “white” individuals in different areas of the world, the focus on sickle-cell anemia as purely a racial disease was challenged. Numerous cases of sickled cells were soon discovered in “white” populations throughout the Mediterranean, Mexico, and Europe.

The sickle-cell disease affects millions of people all across the globe. In the United States, approximately 72,000 people are affected by the disease, with the disease occurring in 1 in 500 African American births and 1 in 1000-1400 Hispanic American births. There are approximately 2 million Americans and 1 in 12 African Americans who are carriers of the sickle-cell trait. In Africa, there is a large variance throughout, with 40% of some tribes having the disease.

It was in 1949 that physical chemist Linus Pauling found that the sickle-cell disease was due to a molecular defect in the hemoglobin molecule. It was a specific point in the molecular composition of hemoglobin that Pauling suggested caused the sickling of red blood corpuscles. Molecular biologists determined that this disease was caused by an error in the amino acid substitution on hemoglobin. This was thought to be the first discovered molecular disease.

Molecular biology shows the importance of amino acid sequences during the formation of proteins. Each altered gene, called an allele, codes for different chemical and bonding interactions during protein formation. An individual who is homozygous for a gene has acquired two copies of one allele, SS (sickle-cell anemia) or AA (normal genotype). If only one sickle allele is inherited, then he or she is heterozygous (AS). In order for someone to have the sickle-cell disease, he or she must inherit the sickle-cell allele from both parents.

Scientists determined that if a child inherited only one copy of the Hb A allele from one parent then he or she was heterozygous and showed no serious health effects. It was also discovered that any individual possessing the sickle-cell trait would be resistant to malaria. Within populations, the advantages of having resistance to malaria are balanced through natural selection by the effects of sickle-cell anemia. Thus, although complex factors are involved, in areas where malaria is prevalent, the population will tend to shift toward selecting the sickle-cell gene for protection and to balance mortality. Biologists came to define this relationship of population genetics as “balanced polymorphism.”

The major symptoms of sickle-cell disease are joint and bone pain, rapid heart rate, decreased respiration and fatigue, ulcers on the lower legs, severe abdominal pain, jaundice, delayed growth, poor vision, and fever. The mortality rate of the sickle-cell disease is highest within the first year of life; therefore, early detection is necessary for increased survival. Doctors commonly use electrophoresis along with a complete blood count (CBC) to determine if Hb S is present. This simple blood test enables doctors to determine the presence of sickle hemoglobin in the patient. In addition, genetic counseling is recommended for all carriers to prevent or discuss the implications of having a child born with sickle-cell anemia.

Although no cure has been discovered for the sickle-cell disease, many new drugs and treatments have been developed to stop the factors that cause the recurring, painful sickling crises. Researchers have found that the inflammatory response causes the cells that line the blood vessels to be sticky. This leads to a build up of sickle cells sticking to endothelial cells that line the blood vessels, eventually causing a blockage. Some studies have shown that anti-inflammatory drugs, such as steroids and ibuprofen, can relieve sickling crises. In addition, blood transfusions increase the red blood cell count, and regular transfusion therapy has been found to help prevent recurring strokes in infants.

The present research shows a promising future for patients with the sickle-cell disease. One future treatment may be in gene transplant, in which a virus is used to transplant a normal gene (hemoglobin A) into the bone marrow cells of a sickle-cell patient (hemoglobin S). Although the goal is for the gene to instruct the bone marrow to produce normal hemoglobin, it has not yet proven successful in humans. Additionally, new vaccines are being designed in hope of fighting infection and early infant death associated with the sickle-cell disease.

The sickle-cell disease affects millions of people throughout the world and its implications must not be overlooked. The medical world has made great strides in research and treatment of this disease. Further genetic analysis in the development of innovative therapeutic agents provides a promising future for sickle-cell patients. With proper treatment and a healthy lifestyle, the life expectancy will continue to increase for patients who are suffering from the sickle-cell disease.

References:

1. Wailoo, K. (2001). Dying in the city of the blues: Sickle cell anemia and the politics of race and health. Chapel Hill: University of North Carolina Press.