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Sickle cell anemia is one of the most common genetic diseases that affects millions globally. It is a genetic disease affecting the red blood cells, more specifically, affecting the oxygen transporting protein found inside RBCs, hemoglobin. Individuals with sickle cell anemia have mutated hemoglobin molecules that can cause RBCs to distort in shape, resulting in a variety of complications.
Genetics Background
The human genome is composed of a huge amount of genetic information in the form of DNA bases coding for life functions such as the synthesis of proteins. The genome is organized into a unique number of DNA molecules in each organism called chromosomes. Humans have 46 chromosomes in total: two sex chromosomes and 44 autosomal (non-sex) chromosomes. We have two copies of each type of chromosome, giving each individual 23 types of chromosomes. Each chromosome contains various genes, sections of DNA coding for specific characteristics or features. There exists multiple versions of each gene, known as alleles; each allele expresses varying forms of a characteristic.
For example, as Gregor Mendel found in his famous experiments, the height gene for pea plants consists of a tall and short allele. Certain alleles can exhibit dominance over others when they are both present. When the gene is expressed, if the dominant allele is present, it masks the trait of the other allele, known as the recessive. Codominance is also possible, where an intermediate trait is expressed. As we inherit half of our chromosomes from each parent respectively, we inherit one allele from our mother and one allele from our father. During the entire life cycle of the individual, DNA undergoes mutations and changes in nitrogenous base sequence occur. Mutations create new, mutated alleles and gives rise to certain genetic diseases.
What is Sickle Cell Anemia
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Individuals with sickle cell anemia have defective hemoglobin molecules inside their RBCs that cause the cell to distort into a “sickle” shape. It is caused by a single base substitution mutation on the gene coding for hemoglobin that causes an amino acid change from glutamic acid to valine. This change from a hydrophilic to hydrophobic amino acid causes changes to the overall structure of the protein and affects its function. The mutated hemoglobin molecules clump together in low oxygen environments and cause the blood cell to distort in shape and become rigid. This causes the RBCs to form clots and cause complications such as heart attacks or strokes. As blood cells return to high oxygen environments, they expand back to their original shapes, damaging the cell membrane and dramatically decreasing the life of a RBC. Thus, they die at a faster rate than the bone marrow can replace them, causing a shortage of RBCs, known as anemia. Sickle blood cells are not able to carry oxygen as effectively, causing there to be insufficient amounts of oxygen in the body.
Sickle cell anemia is an autosomal codominant genetic disorder; this means that when both alleles are present, an intermediate form of the both alleles is expressed. An individual is considered to have sickle cell anemia when they inherit two copies of the recessive mutated allele for hemoglobin. The intermediate form of the disease produces some sickle cells and some normal cells, thus causing less serious form of anemia as there are still a number of regularly functioning RBCs.
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Sickle cell anemia can be diagnosed through blood tests usually conducted at a very young age. Samples of blood can be examined under microscopes in low-oxygen environments to detect the distinct sickle cells. It can also be diagnosed before birth by extracting samples of amniotic fluid or tissue from the placenta. These samples both contain fetal cells that can be screened for the presence of the mutated hemoglobin allele. Parents can test their chances of having children with sickle cell anemia by receiving blood or genetic screening tests to test for the mutated allele. They can decide whether they want to have children after comparing the genotypes (allelic profiles) of both parents. Sickle cell anemia is typically diagnosed during childhood with symptoms appearing at around 5 or 6 months. Infants with sickle cell anemia usually show fatigue due to anemia and swelling of extremities due to poor blood flow. As the patient progresses in life, their symptoms and chances of developing more serious complications may increase. Acute or prolonged pain crises, delayed growth, various organ incompetency, vision problems, and pulmonary hypertension are all potential symptoms patients can experience as they age.
Treatment
Currently, the only definitive cure for sickle cell anemia is stem cell transplant through bone marrow. Blood cells from a suitable donor, usually a family member, are collected to be prepared for transplantation. In the meantime, the individual undergoes treatment such as chemotherapy to kill diseased cells that express the mutated hemoglobin gene. The healthy blood cells are then injected into the patient’s bone marrow to form new RBCs with normal hemoglobin molecules. However, this is a very experimental procedure with many life threatening risks such as rejection. It is only recommended for those with very severe forms of the illness or have developed dangerous complications due to it. Blood transfusions can also be performed to reduce the impact of the disease over time, but it is less effective. Donor blood is collected and healthy RBCs are removed. Cells are transfused intravenously into the patient's body so that as the sickle cells die over time, the proportion of normal cells in the body increases.
For patients with less lethal forms of the disease, treatment usually involves alleviating the symptoms and preventing other conditions from developing. Patients can be prescribed medications to control symptoms of the illness such as decreasing the frequency of pain, dilating blood vessels lessen the effects of clots, preventing infections, and etc. They also have to be more careful in ensuring that they lead a healthy lifestyle and continue regular doctor’s check ups to ensure. Having sickle cell anemia undoubtedly shortens an individual’s life expectancy as it makes them more prone to potentially life threatening complications such as blood clot-related conditions, serious infections, organ failure, and etc. However, under the right care and with regular medical attention, patients can continue to carry out very fulfilling lives.
Article Author: Cindy Zhao
Article Editors: Victoria Huang, Sherilyn Wen
References
Allott, Andrew, and David Mindorff. “Genetic.” IB Biology Course Book: 2014 Edition: Oxford IB Diploma Program, 2014 ed., Oxford University Press, 2014, p. 146.
CDC. “What Is Sickle Cell Disease?” Centers for Disease Control and Prevention, Center for Disease Control and Prevention, 14 Dec. 2020, www.cdc.gov/ncbddd/sicklecell/facts.html.
“Living with Sickle Cell.” Sickle Cell Association of Ontario, 31 May 2019, sicklecellontario.ca/about-sickle-cell/living-with-sickle-cell.
Mayo Clinic. “Sickle Cell Anemia.” Mayo Clinic, 17 July 2021, www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876.
MedlinePlus. “Sickle Cell Disease.” MedlinePlus, National Institute of Health, 1 July 2020, medlineplus.gov/genetics/condition/sickle-cell-disease/#causes
NIH. “Sickle Cell Disease.” NIH, National Heart Lung and Blood Institute, 1 Sept. 2020, www.nhlbi.nih.gov/health-topics/sickle-cell-disease.
Walters, Mark C., et al. “Bone Marrow Transplantation for Sickle Cell Disease.” New England Journal of Medicine, vol. 335, no. 6, 1996, pp. 369–76. Crossref, doi:10.1056/nejm199608083350601.