Sickle Cell Disease (SCD)


A recent study in 2018 disclosed with a high degree of certainty that the point mutation responsible for sickle cell disease (SCD) was a singular event that occurred somewhere in West or Central Africa. This event conferred an evolutionary advantage to that individual, rendering them more resistant to malaria and thus favored the propagation of that gene. These data indicate that the sickle cell mutation sprung into existence approximately 259 generations ago. It is postulated that had it not been for the heterozygous advantage offered by this gene mutation, the βS allele would have been immediately lost instead of passed on.1 This largely explains why SCD is most common in individuals of African descent. 

It is therefore no coincidence that African countries share the largest burden of SCD globally with prevalence rates of up to 2%, with India following suit.2,3 In 2010, more than half (57%) of all newborns with SCD (defined as βS/ βS in that study) were born in 3 countries: Nigeria, the Democratic Republic of Congo (DRC), and India.3  A later study reports that 75% of all SCD patients are born in sub-Saharan Africa.4 Estimating prevalence is challenging due to the scarcity of data in some of the heavily burdened countries. Despite the high health burden of SCD globally, it remains a neglected tropical disease described as “globally invisible” by one report.5,6  

Sickle cell trait (SCT; carrier of one βS allele) reaches prevalence rates of up to 30% in sub-Saharan Africa.2 Isolated populations, such as those seen in western Uganda, reach prevalence rates of 45%, and data from the 1950s and 1960s report rates of up to 55% in select Indian tribal communities.2,5 In the DRC, 12% of children hospitalized in pediatric wards have SCD. Most deaths from SCD occur in children <5 years of age, adolescents, and pregnant women. Unfortunately, in developing countries, robust newborn screening programs are largely lacking, which contributes to mortality in this subset of patients. In countries where neonatal is screening is effectively practiced, such as Benin in West Africa, the under-5 mortality rate for SCD is 10 times lower than the overall SCD under-5 mortality rate.2 

Being born with SCD in a high-income country is associated with better outcomes, and affected individuals live well into adulthood; however, overall survival is less than that of the general population.7 Conversely, more than half of affected children in Africa succumb to their illness before the age of 5 years. Mortality in Africa reaches a staggering 50% to 90% in children with SCD.8  In the United States, the all-cause death rates for patients with SCD between 1983 and 2002 were 0.78 for infants aged 0 to 3 years and 0.43 for children aged 4 to 9 years.9 The advent of the pneumococcal vaccine in 2000 played a major role in reducing mortality.10 Following the introduction of the vaccine, a 68% decrease in mortality was observed in infants 0 to 3 years of age and a 39% reduction was observed in children 4 to 9 years of age.10 

In the United States, it is estimated that SCD affects 100,000 people and that SCT is possessed by 3 million Americans.10,11 Occurrence is approximately 1 in 365 black American births and 1 in 16,300 Hispanic American births. One in 13 black Americans are born with SCT.10 Due to differences in the ethnic and racial makeups between states, prevalence and incidence vary. In Montana, 0.8 cases per 1000 births possess SCT, while that number is approximately 34 cases per 1000 births in Mississippi. In 2010, the incidences of SCT per 1000 births in the United States were 73.1 in black newborns, 3 in white newborns, 6.9 in Hispanic newborns, and 2.2 in Asian or Pacific Islander newborns.12 One study in Michigan reported that approximately 86% of patients with SCD in the study population between 1997 and 2014 were black and 2.5% were white.11 

References

1. Shriner D, Rotimi CN. Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene Wet Phase. Am J Hum Genet. 2018;102(4):547-556. doi:10.1016/j.ajhg.2018.02.003

2. Sickle-cell disease: a strategy for the WHO African Region. World Health Organization. June 22, 2010. Accessed November 10, 2021.

3. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10(7):e1001484. doi:10.1371/journal.pmed.1001484

4. Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020;16(7):380-390. doi:10.1038/s41584-020-0441-1

5. Raman V, Seshadri T, Joice SV, Srinivas PN. Sickle cell disease in India: a scoping review from a health systems perspective to identify an agenda for research and action. BMJ Glob Health. 2021;6(2):e004322. doi:10.1136/bmjgh-2020-004322

6. Lopez AD, Williams TN, Levin A, et al. Remembering the forgotten non-communicable diseases. BMC Med. 2014;12:200. doi:10.1186/s12916-014-0200-8

7. Sedrak A, Kondamudi NP. Sickle cell disease. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed November 10, 2021.

8. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med. 2011;41(6 Suppl 4):S398-405. doi:10.1016/j.amepre.2011.09.013

9. Yanni E, Grosse SD, Yang Q, Olney RS. Trends in pediatric sickle cell disease-related mortality in the United States, 1983-2002. J Pediatr. 2009;154(4):541-545. doi:10.1016/j.jpeds.2008.09.052

10. Data & statistics on sickle cell disease. Centers for Disease Control and Prevention. Accessed November 10, 2021.

11. Reeves SL, Jary HK, Gondhi JP, Kleyn M, Spector‐Bagdady K, Dombkowski KJ. Incidence, demographic characteristics, and geographic distribution of sickle cell trait and sickle cell anemia births in Michigan, 1997-2014. Mol Genet Genomic Med. 2019;7(8):e795. doi:10.1002/mgg3.795

12. Incidence of sickle cell trait in the US. Centers for Disease Control and Prevention. Accessed November 10, 2021.

Reviewed by Debjyoti Talukdar, MD, on 11/11/2021.

READ MORE ON SCD