Sickle Cell disease (SCD) is a group of genetic blood disorders which affect the global population. It affects millions of people worldwide and is most common among people whose ancestors lived in tropical and sub-tropical sub-Saharan regions where malaria is or was common. It is estimated that about 12,500 people in the UK suffer from SCD and on average, 1 in 2,400 babies born in England have the disorder. However, in certain urban areas rates can be drastically higher, such as 1 in 300.
As stated by The World Health Organisation (WHO), SCD adds to 5% of the deaths of children under the age of 5 in some African countries and many children are at risk of premature death. Many of these deaths can be prevented and with advances in treatment, mortality rates have decreased dramatically between the periods of 1983- 1986 and 1999-2000. There was a 68% reduction in mortality rates between ages 0-3, a 39% reduction between ages 4-9 and a 24% reduction between ages 10-14.¹ This essay will mainly focus on the management and treatment of SCD, the advantages and disadvantages of different types of treatments as well as the pathophysiology of SCD.
Genetics & Inheritance
SCD is caused by abnormalities in the haemoglobin (Hb) chain synthesis caused by a single point mutation of the gene HBB. As the synthesis of Hb is an intricate and exceptionally balanced process, there are many possibilities for errors to occur. The different types of errors can lead to structural deformities of the globin chain. Hb is a globular protein molecule comprising of two pairs of polypeptide chains wrapped around one heam molecule. The polypeptide chains (globin chains) vary from alpha (α), beta (β), gamma (γ), delta (δ), epsilon (ε) and zeta (ζ). During intra-urine development different polypeptide chains are being expressed and each will alter the location of erythropoiesis as well as the overall type of Hb molecule synthesized. A single point mutation in the gene coding for Hb leads to SCD. The genetic mutation causes a change in the primary sequence of the amino acid from GAG (glutamic acid) to GTG (valine) causing the synthesis of Sickle haemoglobin (HbS). (Ref)
There are also some other mutations which may occur due to insertions of lysine (AAG) instead of glutamic acid (HbC and HbO Arab) or replacement of glutamine for glutamic acid (HbD Punjab) resulting in other malformations in Hb. These malformations are named this way due to their higher prevalence in those specific regions of the world. When one inherits any of these haemoglobins along with HbS mutation, they will present with clinically significant SCD.
The inheritance of SCD follows Mendelian principles. SCD is autosomal recessive with variable patterns of inheritance, it can either be inherited homozygously or heterozygously if combined with other mutated Hb genes. For example, inheritance of HbS with many different mutations of the genes coding for β-thalassemia results in SCD. A wide range...