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Sickle cell disease is the most common inherited blood disorder in the United States. It affects about 80,000 Americans. In the United States, African Americans are most frequently affected by sickle cell disease. About one in 12 African Americans and about one in 100 Hispanic Americans carry the sickle cell trait.
What Causes Sickle Cell Disease?
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Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene. This gene is responsible for the creation of a protein called beta-globin. Beta-globin is part of a larger protein called hemoglobin that is found in red blood cells. Figure 1 shows how a single gene mutation causes a significant change to the beta-globin protein units that form the structure of hemoglobin.
Figure 1 – A single mutation in the D-N-A sequence of a gene results in a significant change in the shape of the red blood cell. For a normal cell and a sickle cell, the following parts are described: partial D-N-A sequence of hemoglobin-beta gene, partial R-N-A sequence, partial amino acid sequence for beta-globin protein, hemoglobin molecule, and a cross-section of a red blood cell. Normal – partial D-N-A sequence is C-C-T bonds with G-G-A, G-A-G bonds with C-T-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-A-G, G-A-G; Partial amino acid sequence is pro, glu, glu; Hemoglobin molecule is 4 circles forming a square and shaded light and dark, alternatively; cross-section of a red blood cell is half-a-disk with dots labeled normal hemoglobin. Sickle cell – partial D-N-A sequence is C-C-T bonds with G-G-A, G-T-G bonds with C-A-C, G-A-G bonds with C-T-C; partial R-N-A is C-C-U, G-U-G, G-A-G; Partial amino acid sequence is pro, val, glu; Hemoglobin molecule is 3 sets of 4 circles forming a crooked square and shaded light and dark, alternatively; cross-section of a red blood cell is a flat, long half-disk with dots labeled abnormal hemoglobin forms strands that cause sickle shape.
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Normally, A is the fifth letter in the DNA sequence for this part of the hemoglobin-Beta gene. See the top line of letters in figure 1. This coding normally specifies the amino acid glutamic acid (Glu) in that place in the beta-globin protein. If the A changes to a T, the new amino acid specified in that place is valine (Val). This change in the beta-globin protein leads to an abnormally long hemoglobin molecule.
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In people with sickle cell disease, abnormal hemoglobin molecules—hemoglobin S—stick to one another. They form long, rod-like structures. These structures cause red blood cells to become stiff. They assume a sickle shape. Red blood cells with normal hemoglobin (hemoglobin-A) are smooth and round. They easily glide through blood vessels. The sickle shape causes the red blood cells with abnormal hemoglobin to pile up.
Effects of Sickle Cell Disease
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Sickle cells are destroyed rapidly in the bodies of people with the disease. This causes anemia, a shortage of healthy red blood cells. Anemia can produce symptoms such as pale skin, weakness, and headaches. Severe cases of anemia can lead to heart attacks. This anemia is what gives the disease its commonly known name—sickle cell anemia.
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Sickle cells that pile up can cause blockages and damage vital organs and tissue. Sickle cells can result in lung tissue damage that causes a condition called acute chest syndrome. These abnormal cells also damage the spleen, kidneys, and liver. Damage to the spleen makes patients—especially young children—easily overwhelmed by bacterial infections.
Inheritance of Sickle Cell Disease
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A baby born with sickle cell disease inherits the mutated hemoglobin-Beta gene for the disorder from both parents. When both parents have the genetic defect, there is a 25 percent chance that each child will be born with sickle cell disease.
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If a child inherits only one copy of the defective gene (from either parent), there is a 50 percent chance that the child will carry the sickle cell trait. People who only carry the sickle cell trait typically don't get the disease. However, they can pass the defective gene on to their children.
Diagnosing Sickle Cell Disease
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Doctors diagnose sickle cell disease through a blood test that checks for hemoglobin S—the defective form of hemoglobin. To confirm the diagnosis, a blood sample is examined under a microscope to check for large numbers of sickled red blood cells. In more than 40 states, testing for the defective protein that causes people to develop sickle cell disease is routinely performed on newborns.
Gene Therapy: Hope for a Cure
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Researchers are experimenting with attempts to cure sickle cell disease using gene therapy. They correct the defective gene and then insert it into the bone marrow of those with sickle cell disease. This, they hope, will prompt the body to produce normal hemoglobin. Recent experiments show promise. In December 2001, scientists at Harvard Medical School and MIT announced that they had corrected sickle cell disease in mice using gene therapy.
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Researchers bioengineered mice so that their genetic material contained the defective human hemoglobin-Beta gene that causes sickle cell disease. Bone marrow containing the gene was removed from some of the mice and genetically "corrected." This was done by adding a copy of the human hemoglobin-Beta gene that researchers altered. This altered gene inhibits the production of abnormal hemoglobin that causes cells to assume a sickle shape.
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Then, researchers removed the bone marrow from some of the other bioengineered mice. The “corrected” marrow was transplanted into these mice. The mice with sickle cell disease began producing high levels of normal red blood cells. They also showed a large reduction in sickle cells. Scientists are hopeful that this technique could also be used to help people with sickle cell disease.
Constructed Response Question
Some effects of sickle cell disease are mentioned in the text. These and other major health complications associated with sickle cell disease are due to the effect of the disease on various body systems. The circulatory system is most directly affected, but this system interacts with all of these body systems by transporting oxygen and nutrients to cells and by carrying waste away from the cells. The table below includes information about some of these other systems in the human body.
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Identify TWO body systems other than the circulatory system that can be affected by sickle cell disease, according to the text.
For each body system, explain why it would be affected and why that would lead to a health complication.
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According to the text, two body systems other than the circulatory system that can be affected by sickle cell disease are the respiratory system and the immune system.
Respiratory System
Why it would be affected: The text mentions that sickled red blood cells can cause blockages in blood vessels, which can lead to lung tissue damage. This damage can result in a condition called acute chest syndrome.
Health Complication: The accumulation of sickled red blood cells can obstruct blood flow to the lungs, impeding oxygen exchange. This would lead to a reduced ability for the body to obtain oxygen, resulting in shortness of breath, chest pain, and discomfort during physical activity, which can severely impact overall respiratory function and health.
Immune System
Why it would be affected: The spleen, which plays a vital role in filtering blood and fighting infections, is particularly susceptible to damage from sickled cells. The text states that damage to the spleen makes patients, especially young children, more vulnerable to bacterial infections.
Health Complication: A compromised spleen leads to decreased immune function and an increased risk of severe infections. Children with sickle cell disease can experience life-threatening infections, which can complicate their health and potentially lead to hospitalization or other serious health challenges.
Overall, sickle cell disease has far-reaching effects that compromise multiple body systems, ultimately affecting a patient's quality of life.
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