Sickle Cell Anemia

A change, or mutation, in a gene can alter the formation or function of its product. In the case of sickle cell hemoglobin, the gene that carries the blueprint for beta-globin has a minute alteration that makes it different from the normal gene. This mutation affects a single nucleic acid along the entire DNA strand that makes up the beta-globin gene. (Nucleic acids are the chemicals that make up deoxyribonucleic acid, known more familiarly as DNA.) Specifically, the nucleic acid, adenine, is replaced by a different nucleic acid called thymine.

Because of this seemingly slight mutation, called a point mutation, the finished beta-globin molecule has an amino acid substitution: valine occupies the spot normally taken by glutamic acid. (Amino acids are the building blocks of all proteins.) This substitution creates a beta-globin molecule—and eventually a hemoglobin molecule—that does not function normally.

Normal hemoglobin, referred to as hemoglobin A, transports oxygen from the lungs to tissues throughout the body. In the smallest blood vessels, the hemoglobin exchanges the oxygen for carbon dioxide, which it carries back to the lungs for removal from the body. The defective hemoglobin, designated hemoglobin S, can also transport oxygen. However, once the oxygen is released, hemoglobin S molecules have an abnormal tendency to clump together. Aggregated hemoglobin molecules form strands within red blood cells, which then lose their usual shape and flexibility.

The rate at which hemoglobin S aggregation and cell sickling occur depends on many factors, such as the blood flow rate and the concentration of hemoglobin in the blood cells. If the blood flows at a normal rate, hemoglobin S is reoxygenated in the lungs before it has a chance to aggregate. The concentration of hemoglobin within red blood cells is influenced by an individual's hydration level—that is the amount water contained in the cells. If a person becomes dehydrated, hemoglobin becomes more concentrated in the red blood cells. In this situation, hemoglobin S has a greater tendency to clump together and induce sickle cell formation.