الفهرس 
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Abstract
Sickle cell disease (SCD) is classified as one of the main hemoglobin disorders, and in recent years it had been known to have a global impact by the World Health Organization (WHO). It comprises a group of inherited red blood cell conditions that result from the synthesis of variant or mutant hemoglobin.
It has remarkable public health implications for Africa. It constitutes 5% of ”under-five deaths”, with up to 16% in West Africa. It forms a significant problem in many countries due to its chronic nature, with no prospect of cure that makes it an important cause of morbidity and mortality.
It has been difficult to identify young children with sickle cell disease who are at highest risk of adverse outcomes before their irreversible organ damage has occurred; patients with SCD are far less likely to be screened for end organ damage than patients with thalassemia, despite a similar transfusion history.
There is a complex network of associations between laboratory tests and clinical events that modulate the risk of death in sickle cell disease. Renal insufficiency, leukocytosis, and the intensity of the hemolytic anemia are related to the severity of sickle cell disease and death.
Although drug and transfusion therapies improve the quality and duration of life of many individuals, developing curative treatments for SCD remains the desired goal. The only curative therapy is hematopoietic stem cell (HSC) transplantation,
Hydroxyurea has also been found to be very effective in reducing the sickling process and consequently the frequency of pain and hospitalizations experienced by patients.
Induction of Hb F can reduce the severity of SCA. Hydroxyurea (HU) is FDA approved for treatment of SCA its administration may increase steady-state Hb F levels and consequently total hemoglobin (Hb) levels in SCA patients. This occurrence may, in turn, account for the reduction in transfusion requirements of a large proportion of these patients following HU treatment.
The level of fetal hemoglobin (Hb F) is inherited as a quantitative trait and is of enormous clinical relevance, given its role in ameliorating the severity of sickle cell anemia. It is regulated by three major loci: Xmn I polymorphism, HBS1L-MYB inter genic region on 6q23.3 and Another QTL is located in in tron 2 of the BCL11A gene on 2p16.1, encoding a transcription factor that mediates γ- to β-globin switching during erythroid development. Together these three loci are responsible for 20-50% of Hb F trait variance
Variation at BCL11A gene is estimated to explain ~15% of the variance in H b F levels and several SNP s have been identified within BCL11A as the most highly associated with the H b F , including rs11886868, rs766432, rs7606173, rs4671393 and rs1427407.
A correlation might exist between BCL11A and HU-mediated Hb F induction pathway. Firstly, this locus affects baseline Hb F levels, and some reports suggest that higher pre-therapy Hb F levels may lead to a more favorable HU response. Furthermore this QTL may influence the severity of disease.
Aim of the work
The aim of the present study was to identify BCL11Apolymorphism in sickle cell anemia patients and to assess its relation if any, to the response to hydroxyurea therapy.
Subjects and methods
This study was carried out on a total of 50 children (3-15 yrs.) suffering from sickle cell anemia or sickle thalassemia and received hydroxyurea treatment for at least 6 months (6-60 months). All patients were subjected to full history taking, complete clinical examination and investigations. The investigations included CBC, liver functions tests, renal functions tests, serum ferritin, hemoglobin electrophoresis and identification of genetic variant (rs11886868 BCL11A SNP).