An Overview of Disease and Health Research Vol. 11

Sickle cell disease (SCD) is a hereditary haematological disorder associated with significant morbidity and mortality, characterised by a wide spectrum of clinical complications that vary across age groups. The disease predominantly affects individuals from sub-Saharan Africa and their descendants, but it is also prevalent in parts of the Mediterranean, the Middle East, and India, with global distribution influenced by migration patterns. SCD encompasses a group of disorders caused by the presence of haemoglobin S. The HbS component of total haemoglobin 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, explaining the reduced water solubility and altered molecular organisation of HbS compared to normal haemoglobin. 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 haemoglobin variants (SCD-S/D, SCD-S/OArab, SCD-S/Lepore). 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 review aims to summarise and critically evaluate recent advances in the treatment of sickle cell disease in children, with a particular focus on novel pharmacological agents, gene-based therapies, and targets for increasing fetal haemoglobin levels. Recent developments in treatment include agents such as voxelotor, hydroxyurea, and crizanlizumab, as well as innovative approaches like CRISPR/Cas9 gene editing and HbF induction therapies. These strategies offer promising improvements in disease management and patient outcomes. The overall clinical burden of SCD remains substantial, underscoring the importance of continued research to improve therapeutic strategies and patient outcomes.