Objectives
- Identify the cause, inheritance pattern and population frequency of sickle cell trait.
- Differentiate sickle cell trait from sickle cell disease.
Statistics of Sickle Cell Trait and Sickle Cell Disease
Sickle cell disease is one of the most common serious inherited disorders in the United States. According to the National Heart Lung and Blood Institute (NHLBI), more than 70,000 Americans and over 6,000 persons in Texas have sickle cell disease. Since 1983, babies in Texas with sickle cell disease have been identified by newborn screening performed by the Department of State Health Services (DSHS).
Approximately 3 million Americans have sickle cell trait, (Kark, 2000). The trait is common among individuals of African ancestry but it can also occur in individuals of Mediterranean, Middle Eastern, Asian Indian, and Hispanic heritage as well as other ethnicities.
Population Frequencies — The Origins and Distribution of Sickle Cell Trait and Disease
The sickle cell mutation in one of the hemoglobin genes proved to be an advantage in people living in countries where malaria was an epidemic, approximately 2,000 years ago. Research reported in The Lancet (Aidoo et al., 2002), found that people who carry a single copy of the sickle cell mutation or sickle cell trait, are at somewhat lower risk for developing malaria although individuals with sickle cell disease can be severely affected. Over time, people with sickle cell trait migrated to other continents and the trait spread. Today people of different ethnic backgrounds or origins can have sickle cell trait including Hispanics, Greeks, Italians, East Indians, Saudi Arabians, Asians, Syrians, Turks, Cypriots, Sicilians, Caucasians, and others. African Americans have the highest rate of sickle cell disease and sickle cell trait.
In the United States, sickle cell disease occurs in 1:500 African Americans (Southwestern Comprehensive Sickle Cell Center, 2007). Sickle cell disease occurs in many other races and ethnicities, also. Sickle cell disease occurs in 1:58,000 Caucasians, 1:1,100 Hispanics (eastern states), 1: 32,000 Hispanics (western states), 1:11,500 Asians, and 1:2,700 Native Americans. About 1:12 African Americans carry sickle cell trait.
However, an individual's race or ethnicity should not be a reason to avoid screening for sickle cell trait. It can be found in people of all backgrounds. Approximately 7% of the world population carries a mutation potentially associated with sickle cell disease and other hemoglobin diseases (Higgs, Steinberg & Nagel, 2001). The Council of Regional Networks for Genetic Services (CORN) has estimated that 1 in 2,500 to 1 in 2,000 newborns in the United States are affected by Sickle Cell Disease (1995).
Hemoglobin Structure
To understand sickle cell trait and sickle cell disease, you must first understand the structure and function of hemoglobin. Hemoglobin is a protein found in all red blood cells that carries oxygen from the lungs to tissues and organs throughout the body. Hemoglobin is made up of 4 globin chains, usually 2 beta-like and 2 alpha chains. Many different hemoglobin types have been described (this is not the same as blood type). The majority (95%-98%) of hemoglobin in healthy adults is called Hemoglobin A (A for Adult; composed of beta2 alpha2 globin chains), (Hemoglobin Variants, 2009). Red blood cells with Hemoglobin A are soft, smooth and round and can easily move throughout the body delivering oxygen to tissues and organs. In newborn babies, Hemoglobin F (F for Fetal; composed of gamma 2alpha2 globin chains) is the most prevalent hemoglobin type. Prior to birth, the fetus begins to undergo a developmental switch with decreasing production of Hemoglobin F and increasing production of Hemoglobin A, which continues until the typical adult hemoglobin pattern is reached at about six months of age.
Introduction to Sickle Cell Disease
Diseases caused by abnormal hemoglobins are called “hemoglobinopathies.” Sickle cell anemia, the most common form of sickle cell disease, is a hemoglobinopathy caused by a mutation of both beta globin genes resulting in an abnormal form of hemoglobin, hemoglobin S (S for sickle). Hemoglobin S changes the characteristics of the red blood cell, making it easily deformable and sticky. Under certain circumstances, red blood cells with hemoglobin S can change to a “sickle” shape, which is easily seen under the microscope, thus giving the name to the disease. The abnormal red blood cells may reduce blood flow to tissues and organs, causing the complications of sickle cell disease.
Hemoglobin S trait may combine with another type of hemoglobin trait (C, D, E, or other clinically significant hemoglobin variant), or beta thalassemia mutation, causing different forms of sickle cell disease. Beta thalassemia mutations are quantitative hemoglobinopathies that result in a reduction in the amount of normal hemoglobin A being produced.
There are several types of sickle cell disease. Homozygous Hemoglobin SS, historically called sickle cell anemia, is the most common. Other types of sickle cell disease include Hemoglobin SC disease and Hemoglobin S beta thalassemia disease. If the beta thalassemia mutation results in no beta-globin production, Hemoglobin A is completely absent and the sickle cell disease is called sickle beta zero thalassemia. If the beta thalassemia mutation results in some degree of beta-globin production, Hemoglobin A can be produced, and the sickle cell disease is called sickle beta plus thalassemia. Some types of sickle cell disease can cause more problems than others. For example, Hemoglobin SC disease is perceived as causing milder symptoms than Hemoglobin SS. Because beta thalassemia mutations may result in almost no Hemoglobin A production to only a mild decrease in Hemoglobin A production, Hemoglobin S beta plus thalassemia can appear to have almost no symptoms, even no laboratory evidence of anemia. However, under stress such as hypoxia or infection, patients with Hemoglobin S beta plus thalassemia may become as ill as a child with Hemoglobin SS. Sickle cell disease can also affect different people in different ways, so it may be hard to know how serious it will be for a particular person. Some patients may also continue to produce increased levels of fetal hemoglobin or Hemoglobin F, which also modifies disease severity.
Introduction to Sickle Cell Trait
Every person has two chromosomes with genes coding for hemoglobin – one inherited from the mother and one from the father. Sickle cell trait occurs when a person has one gene coding for the common adult hemoglobin, Hemoglobin A, and the other coding for Hemoglobin S. It is important to note that sickle cell trait is NOT Sickle Cell Disease — and sickle cell trait will not turn into sickle cell disease as a person gets older. Usually, people with sickle cell trait do not have any medical problems and lead normal lives.
Inheritance Patterns
Because the inheritance of hemoglobin type is autosomal recessive, it is extremely important to know if both parents have sickle cell trait. If so, there is a 25% chance with each pregnancy that the baby may be born with sickle cell disease, specifically Hemoglobin SS. That leaves a 50% chance that their baby will be born with sickle cell trait or one copy of Hemoglobin S and a 25% chance that their baby will not inherit any copies of Hemoglobin S. View an example.
If both parents have normal hemoglobin, there is no possibility that the children will have sickle cell trait or sickle cell disease.
If one parent has sickle cell trait and the other parent has normal hemoglobin, there is a 50% chance with each pregnancy that the child will be born with sickle cell trait, or one copy of Hemoglobin S.