Objectives

  • Identify the cause, inheritance pattern, and population frequency of sickle cell trait.
  • Differentiate sickle cell trait from sickle cell disease.

Hemoglobin Structure

To understand sickle cell disease and sickle cell trait, 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 four globin chains, usually two beta-like and two alpha chains. The majority (95–98 percent) of hemoglobin in healthy adults is called hemoglobin A (A for Adult—composed of two beta and two alpha globin chains) (American Association for Clinical Chemistry, 2010). Red blood cells with hemoglobin A are flexible and round and move easily throughout the body delivering oxygen to tissues and organs. In newborns, hemoglobin F (F for Fetal—composed of two gamma and two alpha globin chains) is the most prevalent hemoglobin type. Prior to birth, the fetus begins to undergo a developmental switch that decreases production of hemoglobin F and increases production of hemoglobin A. This transformation continues until the typical adult hemoglobin pattern is reached at about 6 months of age.

Introduction to Sickle Cell Trait

Every person has two chromosomes with genetic coding for hemoglobin—one inherited from the mother and one from the father. Sickle cell trait occurs when a person has one gene for the common adult hemoglobin, hemoglobin A, and the other for hemoglobin S.

Approximately 3.5 million Americans have sickle cell trait ( Sickle Cell Initiative, U.S. Department of Health and Human Services, 2011). Sickle cell trait is common among individuals of African ancestry, but it can also occur with regularity in individuals of Mediterranean (especially Greek and Italian), Middle Eastern, Asian, Indian, and Hispanic heritage as well as in other ethnicities.

Case Study

Mary’s infant daughter Mina was diagnosed with sickle cell trait after a review of her newborn screening results. Mary explains to her health-care provider that she tested negative and that her husband’s family does not have any known cases of sickle cell trait.

How is it possible for the baby to have sickle cell trait if neither parent has signs of the condition?

Your answer is correct!

If the mother was tested and does not carry the sickle cell gene, then the child did not receive it from her. However, her father may be a carrier of the gene and not know it. Each person has to be tested once to know if he or she has sickle cell trait. When people have the sickle cell trait, it means they carry the gene, not that they have the disease.

Sorry, your answer is incorrect.

If the mother was tested and does not carry the sickle cell gene, then the child did not receive it from her. However, her father may be a carrier of the gene and not know it. Each person has to be tested once to know if he or she has sickle cell trait. When people have the sickle cell trait, it means they carry the gene, not that they have the disease.

Note

Sickle cell trait is NOT sickle cell disease, and sickle cell trait will not turn into sickle cell disease as a child ages. It is a benign-carrier condition and only on rare occasions do people with sickle cell trait experience any medical problems. Most of them lead completely normal lives.

The Origins and Distribution of Sickle Cell Trait

The sickle cell mutation in one of the hemoglobin genes is an advantage for people living in countries in which malaria is epidemic. The mutation began appearing approximately 2,000 years ago. In a study on the age-specific protection afforded by sickle cell trait against clinical malaria in children living on the coast of Kenya (Williams et al., 2005), the authors conclude that “while malaria protection by sickle cell trait probably involves innate factors, such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity.” However, the mechanism of this resistance remains the subject of considerable debate. According to researchers, “establishing this relationship is difficult because immunity to malaria is hard to measure.” A number of mechanisms have been proposed and are under evaluation.

Illustration used with permission from parasitesinhumans.org.

To learn more, view the article, “An Immune Basis for Malaria Protection by the Sickle Cell Trait,” on the website of the National Center for Biotechnology Information, part of the National Institutes of Health.

Over time, people with sickle cell trait migrated to other continents, spreading the trait. Today, sickle cell trait is found in people of different ethnic backgrounds or origins, including Hispanics, Greeks, Italians, Indians, Saudi Arabians, Asians, Syrians, Turks, Cypriots, Sicilians, Caucasians, and others.

overtime

Map used with permission from the Sickle Cell Information Center.

Note

An individual’s race or ethnicity should not be a reason to avoid screening for sickle cell trait. It may be found in people of all ethnic and racial backgrounds. Approximately 5 percent of the world population carries the gene for sickle cell trait (World Health Organization, 2010). African Americans have the highest rate of sickle cell trait in North America, with about 1 in 12 carrying the gene for sickle cell trait.

Introduction to Sickle Cell Disease

Normal Red Blood Cells and Sickle Cells

Introduction to Sickle Cell DiseaseClick to enlarge an illustration of normal red blood cells and atypical red blood cells caused by sickle cell disease.

Illustration used with permission from the National Heart, Lung, and Blood Institute.

Diseases caused by variant or mutated 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 a variant form of hemoglobin—hemoglobin S (S for sickle). Hemoglobin S changes the characteristics of the red blood cell, making it deformed and sticky. Under certain circumstances, red blood cells with hemoglobin S can change irreversibly to a sickle shape, which is easily seen under the microscope, thus giving the name to the disease. The sickled red blood cells may clump together, blocking blood vessels and reducing blood flow to tissues and organs, resulting in all of the complications of sickle cell disease.

Hemoglobin S trait may combine with another hemoglobin trait (C, D, E, or other clinically significant hemoglobin variant), or a thalassemia mutation, causing different forms of sickle cell disease.

There are several common types of sickle cell disease:

Some types of sickle cell disease cause more problems than others. In general, patients with hemoglobin SC disease have milder symptoms than patients with hemoglobin SS. Some people with hemoglobin S beta plus thalassemia may have almost no symptoms because beta thalassemia mutations may range from almost no hemoglobin A production to only a mild decrease in hemoglobin A production. However, under systemic stress, such as seen with hypoxia or infection, patients with hemoglobin S beta plus thalassemia may become as ill as those with hemoglobin SS. Sickle cell disease can also affect different people in different ways, so it may be difficult to predict how serious someone’s symptoms will be. Some patients may continue to produce increased levels of fetal hemoglobin or hemoglobin F, which may decrease disease severity.

ACT sheets (for providers) and FACT sheets (for parents)

The Texas Department of State Health Services has developed detailed but succinct information sheets and health-care provider action plans for each of the 28 genetic and congenital disorders for which Texas newborns are screened. These are called ACTion (ACT) sheets. DSHS has also created disease-specific information sheets on each of these disorders for you to share with parents or caregivers. These are known as FACT sheets. FACT sheets can be used by providers as talking points, or can be handed out to parents and caregivers by providers. If a newborn you have screened has an abnormal test result, ACT sheets and FACT sheets are critical in helping you determine the next steps to take, including educating the infant’s parents or caregivers about a specific condition.

The ACT sheet should be reviewed and followed in its entirety or as directed by the DSHS Clinical Care Coordinator. However, the most important actions are highlighted in the ACT sheet’s box and include:

The resources below are specific to hemoglobinopathies:

  • Each of these inherited disorders may result in anemia and painful sickling crises. Infants with the same disorder may show variable severity of the disease. Hb SS (sickle cell anemia)ACT Sheet | FACT Sheet
  • Hb S/Β-Thal (hemoglobin S/beta-thalassemia) ACT Sheet | FACT Sheet
  • Hb S/C (hemoglobin S/C disease) ACT Sheet | FACT Sheet
  • Additional educational resources are available on the DSHS Sickle Cell Disease web page.

Sickle Cell Disease Prevalence

Sickle cell disease is one of the most common and serious inherited disorders in the United States. An estimated 70,000–100,000 Americans have sickle cell disease, according to the National Heart, Lung, and Blood Institute (NHLBI, n.d.).

Prevalence of Sickle Cell Disease in the United States

African American 1:500
Hispanic (eastern states) 1:1,100
Native Americans 1:2,700
Asian 1:11,500
Hispanic (western states) 1:32,000
Caucasian 1:58,000

Graph used with permission from the Southwestern Comprehensive Sickle Cell Center, 2007.

In Texas, more than 6,000 people are estimated to have sickle cell disease (Southwestern Comprehensive Sickle Cell Center, n.d.). The Texas Department of State Health Services (DSHS) has been screening for sickle hemoglobin as a part of a newborn screening program since 1983.

On December 22, 2008, the General Assembly of the United Nations adopted a resolution recognizing sickle cell disease as a public health problem (CDC, 2010). As a result, “World Sickle Cell Day” is recognized on June 19 each year to increase awareness about sickle cell disease at the national and international levels. Click this link to the United Nations website to read the complete General Assembly’s announcement.

Case Study

George and Jan are a Caucasian couple. Jan, who is of Italian descent, has beta thalassemia trait. When she was pregnant, her doctor wanted to test her husband. Jan had assumed that because her husband has blond hair and blue eyes, there would be no way he could have thalassemia trait or sickle cell trait. She was surprised when the doctor called with the positive test results. They have just had their first baby, and the infant has blond hair and blue eyes and tested positive for sickle beta plus thalassemia.

How is it possible for George, a blond, blue-eyed Caucasian to have sickle cell trait?

Your answer is correct!

The diagnosis of sickle cell trait is not limited to people of African or Mediterranean heritage or other ethnicities. The combined effects of many genes determine traits such as hair and eye color. George inherited the sickle cell disease gene from either his mother or father, but not both. If he had inherited the sickle cell gene from both parents, he would have sickle cell disease.

Sorry, your answer is incorrect.

The diagnosis of sickle cell trait is not limited to people of African or Mediterranean heritage or other ethnicities. The combined effects of many genes determine traits such as hair and eye color. George inherited the sickle cell disease gene from either his mother or father, but not both. If he had inherited the sickle cell gene from both parents, he would have sickle cell disease.

Inheritance Patterns

Because the inheritance of hemoglobin type is autosomal recessive, it is extremely important to know whether both parents have sickle cell trait, hemoglobins A and S. If they do, there is a 25 percent chance with each pregnancy that the baby will be born with sickle cell disease, specifically hemoglobin SS. That leaves a 50 percent chance that their baby will be born with sickle cell trait or one copy of hemoglobin S, and a 25 percent chance that their baby will not inherit any copies of hemoglobin S and be hematologically normal.

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 percent chance with each pregnancy that the child will be born with sickle cell trait, (one copy of hemoglobin S).

Inheritance Pattern for Sickle Cell Trait

Inheritance

This diagram shows how two parents with sickle cell trait can pass the gene to their children.

Illustration used with permission from the New Jersey Department of Health and Senior Services.

I verify that I’ve read this entire lesson.