New Insights in the Treatment of Sickle Cell Disease in Childhood

Sickle cell disease encompasses diseases that are pathophysiologically caused by hemoglobin S. The HbS component of total hemoglobin in SCD is normally over 50%. HbS is based on an amino acid substitution at position 6 of the β-globin chain, where glutamic acid is replaced by valine. This substitution replaces a hydrophilic amino acid with a hydrophobic amino acid at an outward-facing position in the h molecule, explaining the reduced water solubility and altered molecular organization of HbS compared to normal hemoglobin. Diseases caused by HbS include homozygous SCD, where both alleles are affected by the sickle cell mutation (SCD-S/S), HbSC disease, where one allele is affected by the sickle cell mutation and the other by the HbC mutation (SCD-S/C), and sickle cell β-thalassemia with mixed heterozygosity for the sickle cell mutation and a β-thalassemia mutation (SCD-S/β-thalassemia). In SCD-S/β-thalassemia, forms are distinguished where the β-thalassemia mutation completely inactivates the affected gene (SCD-S/β0-thalassemia) and forms where the allele with the thalassemia mutation still has residual activity (SCD-S/β+-thalassemia). Rarely, the sickle cell mutation can also be combined with other hemoglobin variants (SCD-S/D, SCD-S/OArab, SCD-S/Lepore). The carrier status for the sickle cell mutation generally has no clinical significance except in extreme situations (e.g., eye trauma or surgeries involving cardiopulmonary bypass). Carriers have a normal life expectancy. However, there are individual reports of complications in heterozygous carriers of the sickle cell mutation under common circumstances such as pregnancy, mountain sports, intense physical activity, or air travel. It is also unclear whether the carrier status is associated with an increased rate of kidney complications. Nevertheless, it is not appropriate to indicate specific medical care needs based on these individual case reports given the frequency of carrier status. However, the familial risk of developing SCD should be considered in adult carriers. This manuscript focus on new targets to treat sickle cell anemia in children.