Sickle cell disease (SCD) is an inherited anemia that follows the autosomal recessive (AR) pattern of inheritance requiring two copies of the sickle genetic mutation (one from each parent). A child who inherits the two copies of the sickle mutation will be diagnosed as having sickle cell anemia (with hemoglobinSS, also designated as Hgb SS). One who inherits a copy of a sickle hemoglobin gene mutation from one parent and a normal hemoglobin gene from the other parent will have HgbAS, which renders the child a carrier of the sickle cell trait. It is also possible that a parent may carry a normal copy of the hemoglobin gene and one of the other hemoglobin variants, resulting in the child’s hemoglobin being designated as HgbAC, AD, or AE.

Both parents who carry a normal hemoglobin gene and the sickle cell hemoglobin are usually healthy carriers (heterozygotes) of the sickle trait (HgbAS); they will have inherited this trait, and it is a condition that under normal circumstances will not make them sick. However, under certain conditions (for instance, low oxygen tension at very high altitudes), having the sickle trait can lead to health problems such as hematuria (blood in the urine), pain, splenic sequestration (blood entrapment or pooling of blood in the spleen), and sudden death. Parents who are heterozygote carriers with one copy of the sickle cell gene may have one
copy of the variant hemoglobin genes and may or may not have health problems associated with their carrier status.

Athletes with sickle cell trait (heterozygote carriers of one copy of the sickle cell gene mutation) have been known to develop red blood cell sickling as a result of rhabdomyolosis (destruction of muscle tissue associated with trauma, strenuous exercise, or related events) during uncontrolled training exercises, a condition which could be fatal. According to the 2007 Consensus Statement by the National Athletic Trainer’s Association, nine young athletes have died from exertional sickling during team sports training.

Identification of trait status, prevention, early recognition, and prompt treatment of exertional sickling will reduce mortality. If both parents carry the sickle trait (Hgb AS), each of their offspring has a 25% chance of receiving two copies of the sickle cell mutation (HgbSS) and having sickle cell anemia, a 50% chance of receiving only one copy and being a carrier of the trait (HgbAS), and a 25% chance of receiving the normal gene and having normal hemoglobin (HgbAA).

The majority of forms of SCD involve a missense mutation in the gene for beta globin, a component of the HgbSS molecule resulting in sickle- or crescent-shaped red blood cells that cannot traverse fine capillaries and deliver oxygen to body cells as normal red blood cells do. These sickle-shaped red blood cells clog up the fine circulation in bones and internal organs, leading to pain and damage especially in the spleen, heart, lungs, and kidneys as well as large blood vessels, as may be seen in cerebrovascular accidents associated with strokes (Gelehrter, Collins, and Ginsberg 1998). This sickling phenomenon and the occlusion in blood vessels that results in the above complications can lead to renal insufficiencies (poor kidney function), leg ulcers, and for women with HgbSS, preterm delivery. Additionally, red cell dehydration, endothelial damage, inflammatory response, and erythrocytes damage can lead to avascular necrosis (severe deterioration of body tissue) and even death (Yale, Nagib, and Guthrie 2000; Buchanan, DeBaun, Quinn, and Steinberg 2004).

The lifespan of the sickle-shaped red blood cell (HgbSS) is only between 10 and 20 days compared to120 days for the normal HgbAA. Because of constant red blood cell hemolysis (destruction), SCD is associated with chronic anemia, and leads to joint pain, leg ulcers, pneumonia, infections, acute chest syndrome (a potential life threatening pneumonia-like phenomenon which may require respiratory support; National Heart, Lung, and Blood Institute 2003), and pulmonary hypertension.

Sickle cell anemia (Hgb SS) is the most common of the sickle cell syndromes or diseases; other types include Hgb SC, Hgb SD, and Hgb SBthal. Hemoglobin electrophoresis, a diagnostic test, is the preferred approach for family testing before a confirmatory diagnosis is made. This test may identify some of the other hemoglobin variants that may be present and can modify the diagnosis, course of illness, and management of the patient and other family members, as well as genetic counseling and community support services that are needed.

Today, with preventive care such as prophylactic penicillin until age five (to protect from infections), and lifelong follow-up, persons with SCD can live into their 50s and some have lived into their 60s and 70s. New approaches such as hydroxyurea to increase the somewhat healthier fetal hemoglobin and minimize pain episodes have been very successful in the treatment of some adults and children (Buchanan, DeBaun, Quinn, and Steinberg 2004). Other treatments involving stem cell transplants (Chandler 2006) and other therapies are being investigated today to improve the health and quality of life of those affected.

The incidence of SCD in African Americans is 1 in 600 live births and 1 in 1,000-4,000 live births among Hispanic Americans, affecting about 72,000 persons in the United States. SCD is commonly found in peoples from sub-Saharan Africa, the Mediterranean, the Middle East, and India. About 2 million Americans (about 1 in 12 African Americans) are heterozygote carriers with the sickle trait (National Heart, Lung, and Blood Institute 2003). Newborn screening in most states in the United States, Puerto Rico, and the Virgin Islands detects infants who are affected with SCD (for early identification and management) or who are carriers of the sickle trait.