Sickle Cell Anaemia (SCA) is a disorder caused by a single gene mutation that affects haemoglobin, the oxygen-carrying molecule in red blood cells. If a person inherits one mutated gene, they carry the sickle cell trait but in the vast majority of cases will not develop SCA. But if a person inherits the mutated gene from both parents, then they will develop SCA.
Sickle Cell Anaemia causes red blood cells to become malformed which hinders their flow through the blood vessels.
The mutation causes haemoglobin to polymerise (stick together) which then deforms the red blood cell, causing it to take irregular shapes including a sickle shape. Consequently, these malformed blood cells can’t flow through the blood vessels properly which restricts blood supply to organs. This results in a vast array of problems, primarily hemolytic anemia (low blood caused by destruction of blood cells) and ischemic damage to tissues and organs resulting in frequent periods of severe pain and even organ failure. The acute chest syndrome is a typical example of organ failure in sickle cell disease and one of the leading causes of hospitalisation and death among patients (Piel et al. 2017:1562-1565).
70% of babies born with SCA are born in sub-Saharan Africa, most notably in Nigeria and the Democratic Republic of Congo. Although infant mortality (death before 5) among children with SCA has fallen in developed countries, it is still extremely high in Africa. A 2010 estimate put it at between 50-90% though obtaining accurate statistics on sickle cell in Africa is difficult. Screening newborns for SCA is a vital component to being able to treat it as effectively as possible and this is normal practice in the UK, the US and other developed countries. However, to date no African country has implemented mass screening for the trait though some have conducted trial screenings (Kato et al. 2018:2-3, 10).
Global prevalence of Sickle Cell Anaemia. Africa is the epicentre.
The high prevalence of SCA in Africa is primarily explained by its connection with malaria. The so-called malaria hypothesis was first postulated by western scientists in the early twentieth century. The hypothesis begins by noting that malaria has been around for thousands of years and until recently has resulted in almost-certain death in infancy. These factors mean that it would have played a role in natural selection. Because malaria affects blood cells, any changes the structure of blood cells would also hinder the spread of malaria. Thus, it was hypothesised that genotypes associated with changes to the shape of blood cells should be more common in areas with high malaria prevalence (Luzzatto, 2012).
As discussed, SCA does indeed change the structure of blood cells. In the 1950s, a researcher working in Kenya demonstrated that SCA prevalence correlates closely with Malaria prevalence. He also showed that people with sickle cell trait seemed to contract malaria less frequently. Subsequent research has found that trait carriers can and do contract malaria but rarely the most severe. In fact, they are 90% less likely than non trait carriers to get severe malaria (Kato et al. 2018:2). If they do get malaria, they rarely die from it, even from the more severe kinds. It seems that red blood cells in sickle cell trait carriers do get sick, but they are then removed by white blood cells (Luzzatto, 2012).
This complex relationship between sickle dell and malaria is an example of so-called balanced polymorphism. The mutation can be beneficial or deleterious. It is beneficial in heterozygotes (people who carry only one mutated gene) because it gives them some protection against malaria. But the mutation is deleterious in homozygotes (people who carry two of these mutated genes) because it leads to malfunction and possible destruction of red blood cells which cause unpredictable episodes of intense pain and frequently death.
For African-descended people, getting screened for sickle cell trait is one way of preventing their future offspring from developing SCA. Those who carry the trait could employ assortative mating by avoiding having children with other trait carriers. This kind of preventative behaviour could be promoted in public health messaging in the same way that safe sex guidance is promoted.
References:
Kato G. et al. (2018). Sickle Cell. Nature Reviews Disease Primers volume 4(18010). [Link to abstract: https://www.nature.com/articles/nrdp201810 accessed 2 Sept. 18]
Luzzatto. L. (2012). Sickle Cell Anaemia and Malaria. Mediterranean Journal of Hematology and Infectious Diseases, 4(1). [Link to full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499995/ accessed 2 Sept. 18]
Piel, F. et al. (2017). Sickle Cell Disease. The New England Journal of Medicine, 376(16). [Link to abstract: https://www.nejm.org/doi/full/10.1056/NEJMra1510865 accessed 2 Sept. 18]
This post has first been published on Afroscientific.com