Sickle cell disease (SCD) is a complex disorder that affects the structure and function of haemoglobin, reduces the ability of red blood cells (RBCs) to transport oxygen efficiently, and, early on, progresses to a chronic vascular disorder.
Normal haemoglobin (HbA) comprises 2 β-globin and 2 α-globin chains. Individuals who carry the sickle cell trait have 1 normal β-globin allele and a mutation in the second β-globin allele
In patients with SCD, mutations in both β-globin alleles alter the structure of haemoglobin. When deoxygenated, abnormal haemoglobin undergoes polymerisation resulting in the sickling of RBCs
Foetal, haemoglobin (HbF) is a normal type of haemoglobin expressed until ~6 months of age and in individuals with SCD.3
SCD is caused by a single point mutation in the Hb gene, but results in diverse clinical manifestations (eg, chronic vascular damage, vaso-occlusion, and anaemia).
Sickle Cell Trait
Sickle Cell Anaemia
Other SCD Genotypes
HbA
HbS
HbS
HbS
HbS
Hb Mutation
Individuals with sickle cell trait inherit 1 mutant allele HbS
Individuals with sickle cell anaemia inherit 2 HbS alleles
Individuals inherit 1 HbS allele and another mutant Hb allele
Sickle Cell Trait
HbA
HbS
Sickle cell anaemia
HbS
HbS
Other SCD Genotypes
HbS
Hb Mutation
Monogenic=single point mutation caused by 1 gene.
Pleiotropic=1 gene that causes multiple seemingly unrelated effects/complications.
| Genotype | % of SCD population | % of affected ethnicities |
|---|---|---|
|
HbSS (sickle cell anaemia)7,8 |
~74%-76%a |
~70% of patients of African descent |
|
HbSC7,8 |
~18%-24%a |
~25%-30% of patients of African descent |
|
HbSβ°-thalassemia7,8 |
~1%-6%a |
Most prevalent in people of Eastern Mediterranean or Indian descent |
|
HbSβ+-thalassemia7,8 |
~1%-6%a |
Most prevalent in people of Eastern Mediterranean or Indian descent |
|
HbSD7 |
<1% |
Most prevalent in northern India but occurs worldwide |
|
HbSα+-thalassemia2,3,7 |
N/A |
~30% of patients of African descent ~50% of patients of Middle Eastern or Indian descent |
|
HbAS (sickle cell trait)2,9 |
Should not be classified as a true form of SCD |
~8% of African Americans are carriers of the sickle cell trait |
aBased on 3 large multicentre cohorts of patients with SCD of predominantly African descent in the Americas and the United Kingdom.
The prevalence of SCD varies from region to region, and migration is changing the global picture of this disease10-12
By 2050, the number of people born with SCD is expected to grow by 30% around the world.13
References: 1. Conran N, Franco-Penteado CF, Costa FF. Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin. 2009;33(1):1-16. 2. Steinberg MH. Sickle cell disease and associated hemoglobinopathies. In: Goldman L, Ausiello D, eds, Cecil Medicine, 23rd ed. Philadelphia, PA; Saunders Elsevier; 2008:1217-1226. 3. Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;376(16):1561-1573. 4. Kalpatthi R, Novelli EM. Measuring success: utility of biomarkers in sickle cell disease clinical trials and care. Hematology Am Soc Hematol Educ Program. 2018. 2018;2018(1):482-492. 5. Ballas SK, Gupta K, Adams-Graves P. Sickle cell pain: a critical reappraisal. Blood. 2012;120(18):3647-3656. 6. Habara A, Steinberg MH. Genetic basis of heterogeneity and severity in sickle cell disease. Exp Biol Med (Maywood). 2016;241(7):689-696. 7. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031. 8. Saraf SL, Molokie RE, Nouraie M, et al. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatr Respir Rev. 2014;15(1):4-12. 9. Centers for Disease Control and Prevention. Data & Statistics: Sickle Cell Disease. https://www.cdc.gov/ncbddd/sicklecell/data.html. Accessed March 31, 2019. 10. Data on File. Novartis Pharmaceuticals Corp; 2019. 11. Aliyu ZY, Kato GJ, Taylor J, et al. Sickle cell disease and pulmonary hypertension in Africa: a global perspective and review of epidemiology, pathophysiology, and management. Am J Hematol. 2008;83:63-70. 12. Huttle A, Maestre GE, Lantigua R, and Green N. Sickle cell disease in Latin America and the United States. Pediatr Blood Cancer. 2015; 62(7):1131-1136. 13. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010-2015: modelling based on demographics, excess mortality, interventions. PLoS One. 2013;10(7):1-14.
