الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The thalassemia is the commonest single - gene disorder world- wide. Thalassemia was first recognized by Cooley and Lee in 1925 as a form of severe anemia associated with bone changes in children.
Thalassemia encompasses a spectrum of hereditary anemias characterized by reduced or absent production of one or more of the globin chains.
In Egypt, 1000/1.5 million per year born with thalassemia due to combined effect of higher carrier rate and consanguineous marriages. Carrier rate varies from 6-10%. Both sexes are equally affected and the age at onset of symptoms varies significantly.
Mutations in globin genes cause thalassemias. β- thalassemia affects 1 or both of the β-globin genes. Alpha thalassemia affects the alpha-globin genes. These mutations, by causing impaired synthesis of the globin protein component of hemoglobin (Hb), result in anemia.
Thalassemia syndromes are characterized by varying degrees of ineffective hematopoiesis and increased hemolysis. Clinical syndromes are divided into α- and β-thalassemias, each with varying numbers of their respective globin genes mutated.
Because of the variability in the severity of the fundamental defect, there is a spectrum of clinical severity (minor to major), which considerably influences management.
Inadequate β-globin gene production leading to decreased levels of normal hemoglobin (HbA) and unbalanced α- and β-globin chain production. In β-thalassemia major, α-globin chains are in excess to non–α-globin chains, and α-globin tetramers (α4) are formed and appear as red cell inclusions. The free α-globin chains and inclusions are very unstable, precipitate in red cell precursors, damage the red cell membrane, and shorten red cell survival leading to anemia.
Increased erythroid production. This results in a marked increase in erythropoiesis with early erythroid precursor death in the bone marrow. This is characterized by a lack of maturation of erythrocyte.
The complications that occur with β- thalassemia major or intermedia are related to overstimulation of the bone marrow, ineffective erythropoiesis and iron overload from regular blood transfusions.
Alpha-hemoglobin-stabilizing protein (AHSP) is a small protein that binds specifically to the free alpha globin chain (αHb) of hemoglobin (Hb). The main function of AHSP appears to regulate the stability, folding, and assembly of the αHb subunit.
AHSP is a protein expressed in hematopoietic tissues (bone marrow in humans and fetal liver, spleen, and bone marrow) and exclusively by cells of the erythroid lineage. AHSP forms a stable but reversible complex with free αHb to stabilize its structure and limit its chemical reactivity. This interaction prevents αHb aggregation and precipitation in solution and in live cells and therefore maintains αHb available for incorporation into HbA.
The AHSP-αHb interaction also inhibits ROS production and, therefore, oxidative damage. Indeed, structural analysis of AHSP-αHb complex revealed that AHSP and βHb compete to bind to αHb in the same region, called the α1β1 interface. βHb affinity to αHb is stronger and wins this competition, displacing AHSP to form molecule. Consistent with the role of a molecular chaperone, in addition to its ability to stabilize αHb, AHSP is also able to promote refolding of denatured αHb.
Although β-thalassemia results from reduced βHb synthesis, the pathophysiology of this disease is determined by the level of free αHb chains that cause oxidative damage of red blood cells. The marked variability in clinical severity of β- thalassemia has been attributed to environmental and genetic factors, including hereditary persistence of fetal hemoglobin (HPFH) and coexistence of α-thalassemia.. However, these factors cannot explain the phenotypic variability in many cases of β-thalassemia.
Considering the biological and biochemical properties of AHSP, it is natural to speculate those AHSP mutations leading to its reduced expression or altered function, could modify the clinical characteristics of β-thalassemia and provided the first evidence that AHSP could modulate β-thalassemia
The aim of the present work was to study serum level of alpha hemoglobin stabilizing protein (AHSP) and its relation to severity of β-thalassemia in pediatric patients.
This study was conducted on 42 children aged 2-12 years. They were divided into 2 groups: group І: included 28 patients with β- thalassemia. Thalassemic patients were divided into 2 groups: A: included 14 patients with β- thalassemia major (TM). B: included 14 patients with β- thalassemia intermedia (TI). group II: included 14 healthy children matched for age and sex as control group.
All the patients in this study were assessed by detailed history taking including sex, age at diagnosis, onset and frequency of transfusions and other therapies received in addition to history of any complications. Complete physical examination was done for all studied children including anthropometric measurements (weight, height, span) with special emphasis on thalassemic manifestations and complications