Sickle Cell Anemia Health Article

Sickle cell hemoglobin

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 tiny 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 [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 a single amino acid substitution: valine occupies the spot normally taken by glutamic acid. (Amino acids are the building blocks of all proteins.) This substitution is incorporated into the beta-globin molecule—and eventually returning in 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 occurs 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 of 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.

Affected populations

Worldwide, millions of people carry the sickle cell trait. Individuals whose ancestors lived in sub-Saharan Africa, the Middle East, India, or the Mediterranean region are the most likely to have the trait. The areas of the world associated with the sickle cell trait are also strongly affected by malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. According to a widely accepted theory, the genetic mutation associated with the sickle cell trait occurred thousands of years ago. Coincidentally, this mutation increased the likelihood that carriers would survive malaria outbreaks. Survivors then passed the mutation on to their offspring, and the trait became established throughout areas where malaria was common.

Causes & symptoms

Symptoms typically appear during the first year or two of life. However, some individuals do not develop symptoms until adulthood and may not be aware that they have the genetic inheritance for sickle cell anemia.

Anemia

Sickle cells have a high turnover rate, and there is an ongoing deficit of red blood cells in the bloodstream. Common symptoms of anemia include fatigue, paleness, and shortness of breath. A particularly severe form of anemia—aplastic anemia—occurs following infection with parvovirus. Though temporary, parvovirus infection causes extensive destruction of the bone marrow, bringing production of new red blood cells to a halt. Bone marrow production resumes after 7–10 days, but given the short lives of sickle cells, even a brief shutdown in red blood cell production can cause a major decline in hemoglobin concentrations. This event is called "aplastic crisis."

Painful crises

Painful crises, also known as vasoocclusive crises, are a primary symptom of sickle cell anemia in children and adults. The pain may be caused by small blood vessel blockages that prevent oxygen from reaching tissues. An alternate explanation, particularly with regard to bone pain, is that blood is shunted away from the bone marrow but through some mechanism other than blockage by sickle cells.

These crises are unpredictable and can affect any area of the body, although the chest, abdomen, and bones are frequently affected sites. There is some evidence that cold temperatures or infection can trigger a painful crisis, but most crises occur for unknown reasons. The frequency and duration of the pain can vary tremendously. Crises may be separated by more than a year or possibly only by weeks, and they can last from hours to weeks.

The hand-foot syndrome is a particular type of painful crisis, and is often the first sign of sickle cell anemia in an infant. Common symptoms include pain and swelling in the hands and feet, possibly accompanied by a fever. Hand-foot syndrome typically occurs only during the first four years of life, with the greatest incidence at one year.