Sickle Cell Disease Health Article

Definition

Sickle cell disease describes a group of inherited blood disorders characterized by chronic anemia, painful events, and various complications due to associated tissue and organ damage.

Description

The most common and well-known type of sickle cell disease is sickle cell anemia, also called SS disease. All types of sickle cell disease are caused by a genetic change in hemoglobin, the oxygen-carrying protein inside the red blood cells. The red blood cells of affected individuals contain a predominance of a structural variant of the usual adult hemoglobin. This variant hemoglobin, called sickle hemoglobin, has a tendency to polymerize into rod-like structures that alter the shape of the usually flexible red blood cells. The cells take on a shape that resembles the curved blade of the sickle, an agricultural tool. Sickle cells have a shorter life span than normally-shaped red blood cells. This results in chronic anemia characterized by low levels of hemoglobin and decreased numbers of red blood cells. Sickle cells are also less flexible and more sticky than normal red blood cells, and can become trapped in small blood vessels preventing blood flow. This compromises the delivery of oxygen, which can result in pain and damage to associated tissues and organs. Sickle cell disease presents with marked variability, even within families.

Carriers of the sickle cell gene are said to have sickle cell trait. Unlike sickle cell disease, sickle cell trait does not cause health problems. In fact, sickle cell trait is protective against 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 infection. Survivors then passed the mutation on to their offspring, and the trait became established throughout areas where malaria was common. As populations migrated, so did the sickle cell trait. Today, approximately one in 12 African Americans has sickle cell trait.

Worldwide, it has been estimated that one in every 250,000 babies is born annually with sickle cell disease. Sickle cell disease primarily affects people of African, Mediterranean, Middle Eastern, and Asian Indian ancestry. In the United States, sickle cell disease is most often seen in African Americans, in whom the disease occurs in one out of every 400 births. The disease has been described in individuals from several different ethnic backgrounds and is also seen with increased frequency in Latino Americans—particularly those of Caribbean, Central American, and South American ancestry. Approximately one in every 1000-1400 Latino births are affected.

Causes and symptoms

Humans normally make several types of the oxygen-carrying protein hemoglobin. An individual's stage in development determines whether he or she makes primarily embryonic, fetal, or adult hemoglobins. All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta (or beta-like) globin. Sickle hemoglobin is the result of a genetic change in the beta globin component of normal adult hemoglobin. The beta globin gene is located on chromosome 11. The sickle cell form of the beta globin gene results from the substitution of a single DNA nucleotide, or genetic building-block. The change from adenine to thymine at codon (position) 6 of the beta globin gene leads to insertion of the amino acid valine–instead of glutamic acid–at this same position in the beta globin protein. As a result of this change, sickle hemoglobin has unique properties in comparison to the usual type of adult hemoglobin.

Most individuals have two normal copies of the beta globin gene, which make normal beta globin that is incorporated into adult hemoglobin. Individuals who have sickle cell trait (called sickle cell carriers) have one normal beta globin gene and one sickle cell gene. These individuals make both the usual adult hemoglobin and sickle hemoglobin in roughly equal proportions, so they do not experience any health problems as a result of having the trait. Although traces of blood in the urine and difficulty in concentrating the urine can occur, neither represents a significant health problem as a result of sickle cell trait. Of the millions of people with sickle cell trait worldwide, a small handful of individuals have experienced acute symptoms. In these very rare cases, individuals were subject to very severe physical strain.

When both members of a couple are carriers of sickle cell trait, there is a 25% chance in each pregnancy for the baby to inherit two sickle cell genes and have sickle cell anemia, or SS disease. Correspondingly, there is a 50% chance the baby will have sickle cell trait and a 25% chance that the baby will have the usual type of hemoglobin. Other types of sickle cell disease include SC disease, SD disease, and S/beta thalassemia. These conditions are caused by the co-inheritance of the sickle cell gene and another altered beta globin gene. For example, one parent may have sickle cell trait and the other parent may have hemoglobin C trait (another hemoglobin trait that does not cause health problems). For this couple, there would be a 25% chance of SC disease in each pregnancy.

Normal adult hemoglobin transports oxygen from the lungs to tissues throughout the body. Sickle hemoglobin can also transport oxygen. However, once the oxygen is released, sickle hemoglobin tends to polymerize (lineup) into rigid rods that alter the shape of the red blood cell. Sickling of the red blood cell can be triggered by low oxygen, such as occurs in organs with slow blood flow. It can also be triggered by cold temperatures and dehydration.

Sickle cells have a decreased life span in comparison to normal red blood cells. Normal red blood cells survive for approximately 120 days in the bloodstream; sickle cells last only 10–12 days. As a result, the bloodstream is chronically short of red blood cells and hemoglobin, and the affected individual develops anemia.

Sickle cells can create other complications. Due to their shape, they do not fit well through small blood vessels. As an aggravating factor, the outside surfaces of sickle cells may have altered chemical properties that increase the cells' 'stickiness'. These sticky sickle cells are more likely to adhere to the inside surfaces of small blood vessels, as well as to other blood cells. As a result of the sickle cells' shape and stickiness, blockages form in small blood vessels. Such blockages prevent oxygenated blood from reaching areas where it is needed, causing pain as well as organ and tissue damage.

The severity of symptoms cannot be predicted based solely on the genetic inheritance. Some individuals with sickle cell disease develop health-or life-threatening problems in infancy, but others may have only mild symptoms throughout their lives. Individuals may experience varying degrees of health at different stages in the life cycle. For the most part, this clinical variability is unpredictable, and the reasons for the observed variability can not usually be determined. However, certain types of sickle cell disease (i.e. SC disease) tend to result in fewer and less severe symptoms on average than other types of sickle cell disease (i.e. SS disease). Some additional modifying factors are known. For example, elevated levels of fetal hemoglobin in a child or adult can decrease the quantity and severity of some symptoms and complications. Fetal hemoglobin is a normally occurring hemoglobin that usually decreases from over 90% of the total hemoglobin to under 1% during the first year of life. This change is genetically determined, although some individuals may experience elevated levels of fetal hemoglobin due to variation in the genes that control fetal hemoglobin production. Such individuals often experience a reduction in their symptoms and complications due to the ability of fetal hemoglobin to prevent the polymerization of sickle hemoglobin, which leads to sickling of the red blood cell.

There are several symptoms that warrant immediate medical attention, including the following:

• signs of infection (fever greater than 101°F or 38.3°C, coughs frequently or breathing trouble, unusual crankiness, feeding difficulties)
• signs of severe anemia (pale skin or lips, yellowing of the skin or eyes, very tired, very weak)
• signs indicating possible dehydration (vomiting, diarrhea, fewer wet diapers)
• other signs (pain or swelling in the abdomen, swollen hands or feet, screams when touched)

These can be signs of various complications that occur in sickle cell disease.