الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 61 |  |  |
| | | from | 61 | | |
Abstract
Thalassemia considered as heterogeneous group of hemoglobin disorders caused by absent or decreased production of normal globin chains. And considered the most common recessive diseases worldwide; about 1–5% of the global population are carriers of a thalassemia genetic mutation (72).
Thalassemias are frequent in the Middle East, in southeastern and southern Asia, in North and Central Africa and in the Mediterranean countries; however, because of migration, thalassemias are becoming increasingly common in North America and North Europe (73).
Depending on the defective globin chain and on the underlying molecular defects; Thalassemias can be broadly characterized as α- or β -thalassemias, they are recessive traits; thus, the clinical relevant phenotypes result from homozygosity or double heterozygosity for different globin gene defects. They can also manifest from co-inheritance of thalassemia trait and structural hemoglobin variants such as hemoglobin S, C, and E (72).
Ineffective Erythropoiesis in individuals with beta-thalassemia reflects the results of excess and unpaired alpha-globin, the degree of imbalance in the alpha-globin versus beta-globin biosynthetic ratio is the major determinate of disease severity rather than the under production of hemoglobin (16).
Beta-thalassemia is caused by either reduced (beta1) or absent (beta 0) synthesis of the beta globin chains of the hemoglobin (Hb) tetramer, which is normally made up of two alpha globin and two beta globin chains (alpha2beta2). (11).
In patient with beta-thalassemia trait there is a two fold excess in the synthesis of alpha-globin, which is consistent with fairly normal hematopoiesis with only mild microcytosis and hypochromia of the red cells. In individuals with thalassemia intermedia the alpha to non-alpha biosynthetic ratio is typically 3–1/4 because residual capacity for beta-globin synthesis along with usually modest but variable gama-globin synthesis mitigates the consequences of excessa-globin production. Individuals with b0-thalassemia mutations have marked chain biosynthetic imbalance as the underlying basis for their severe phenotype. (17).
When the beta globin chains are reduced or absent, within the red blood cell precursors, the unassembled alpha chains precipitate and lead to oxidative damage of the cell wall, resulting in apoptosis (ineffective erythropoiesis). (15).
Improvement of survival of patients with β-thalassemia, allowed several clinical morbidities to manifest, including renal complications. Patients may experience abnormalities in glomerular filtration rate and dysfunctions in proximal tubules (74).
Serum creatinine is an unreliable indicator of renal functions, as muscle mass, protein intake and hepatic disease affect serum creatinine levels (75).
β-2 microglobulin and Cystatin-C are both specific and sensitive early biomarkers for monitoring tubular and glomerular dysfunction in children with β-TM. (68).