Generalities
Sickle-cell disease (SCD) is a chronic systemic condition that gathers a cluster of erythrocyte
disorders, affecting specifically the hemoglobin gene1-2. This disease is characterized by
acute pain events and gradual organic dysfunction and it is the most common hereditary
monogenic condition in the world, mostly prevalent in Sub-Saharan Africa1-4.
SCD physiopathology
This autosomal recessive condition is due to a mutation in the β-globin gene, located in
chromosome 11, in which the 17th nucleotide is mutated from thymine to adenine
converting the sixth amino acid, glutamic acid, into valine1, 3, 5 and producing an abnormal
hemoglobin form called Hemoglobin S (HbS). As a consequence of this alteration, a
hydrophobic site in the deoxygenated HbS isoform is generated, creating a link between two
β-globin chains, and thus causing polymerization1, which leads to erythrocyte rigidity and
fragility2-4, 6-7.
Three main genotypes cause the SCD: the most common is homozygosity for the βs allele
(HbSS) also called sickle-cell anemia (SCA), followed by heterozygous states HbSC and HbS/β-
thalassemia1, 8. There are other genotypes combining the βs allele with other β-globin point
mutations leading to sickling of erythrocytes and to SCD, but these forms are less prevalent.
All of the above mentioned types are grouped into SCD. The protective advantage of the βs
carrier state over malaria explains the endemic nature of SCD in Sub-Saharan Africa4. There
are five main haplotypes of the βs-globin gene according to the geographical origin. They are
named Benin, Cameroun, Senegal, Central African Republic and Arab-Indian, which are
related with different levels of fetal hemoglobin (HbF)9. A higher HbF level is a protective
factor of SCD complications4.