Sep 154 min read

Sickle Cell Anemia— A Substitution Mutation in Colored Communities

Written By Juanna Maisie John

An Overview:

Sickle cell anemia, known as sickle cell disease (SCD), is a genetic condition affecting the shape of red blood cells. Normal red blood cells are in a biconcave disc shape, allowing maximum oxygen-carrying capabilities and ease of travel through blood vessels. However, individuals with SCD have sickle-shaped blood cells, which cause many complications. Roughly 20 million people globally suffer from sickle cell anemia, and yet most people who have this disease are of African descent. This begs the question as to why SCD is common in African communities.Sickle cell anemia, known as sickle cell disease (SCD), is a genetic condition affecting the shape of red blood cells. Normal red blood cells are in a biconcave disc shape, allowing maximum oxygen-carrying capabilities and ease of travel through blood vessels. However, individuals with SCD have sickle-shaped blood cells, which cause many complications. Roughly 20 million people globally suffer from sickle cell anemia, and yet most people who have this disease are of African descent. This begs the question as to why SCD is common in African communities.

Causes:

To understand the prevalence of SCD across African communities, one must first understand what causes SCD. Sickle cell disease is due to a point mutation in the gene that codes for hemoglobin (the protein that carries oxygen on red blood cells). In sickle cell anemia, the sixth amino acid is altered from glutamic acid to valine. This type of mutation, in which only a single amino acid is swapped, is classified as a point substitution mutation; point since only one amino acid is changed and substitution because an incorrect amino acid is added. Since this change affects the genome, it can be inherited.

SCD is an autosomal recessive disease, only manifesting if the person has two copies of the gene. Individuals with only one copy of the sickle cell trait will become carriers, therefore not displaying the complications themselves.

Pain Phenotype Development:

While SCD is a genetic condition, most patients don’t feel pain until they are 5 to 6 months old. While this phenomenon isn’t fully understood, many researchers hypothesize that this gap in pain may be due to fetal hemoglobin. SCD does not affect fetal hemoglobin, which may be why newborns with sickle cell disease don’t experience any pain caused by it.

Symptoms:

Having sickle-shaped blood cells can present a plethora of painful problems. Sickle-shaped red blood cells die (hemolysis) faster causing jaundice. Since the red blood cells in SCD are deformed they carry a lower amount of oxygen ensuring in lesser energy produced by the body. The lack of energy leads to anemia and bouts of lethargy. Chronic pain and vaso-occlusive episodes are also attributed to SCD since sickle-shaped red blood cells can supply small blood vessels to vital parts of the body such as the heart and joints. Vaso-occlusive episodes can be exacerbated by decreases in temperature since that causes blood vessels to constrict, resulting in a larger number of sickle-shaped red blood cells getting trapped. Sickle-shaped red blood cell clots can also develop into deep vein thrombosis, increasing the chances of developing pulmonary embolisms. Another effect of sickle cell disease is splenic sequestration. Splenic sequestration is when sickle-shaped red blood cells get caught in the spleen and cause inflammation.

Treatment:

While there are many symptoms and complications associated with SCD, there are also various methods to treat it. Hydroxyurea is one of the primary medications given to treat SCD. Hydroxyurea lowers sickling and reduces the number of pain episodes associated with SCD. Voxelotor is another drug that prevents sickle-shaped red blood cells from clotting together. To manage the pain that comes with SCD, over-the-counter drugs and opioids are usually taken. In some severe cases, blood transfusions are used to lower the risk of stroke in sickle cell disease patients. However, the only complete cure for sickle cell disease until recently was a blood and bone marrow transplant. However, due to the high risk and pain associated with these transplants, many are not receptive to this idea. A novel form of treatment pioneered to cure genetic conditions is genetic therapy. Genetic therapy seeks to alter DNA to cure genetic conditions such as SCD.

Prevalence in Colored Populations:

Now to the main question at hand: why is sickle cell disease much more prevalent in African populations than in any other racial population? The answer to this question is related to the incidence of malaria in Africa. Malaria is a disease transmitted by mosquitoes that infects red blood cells. Some symptoms of malaria include fever, diarrhea, fatigue, and even death. Since malaria is such a devastating disease, sickle cell traits developed as an evolutionary response. The presence of sickle cell traits can prevent infection from the malaria pathogen.

Malaria is most common in regions of Africa, which is why SCD affects people of African descent disproportionately.