Alpha Thalasemia


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TMU Univrsity
Alpha Thalassemia

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Alpha Thalasemia

  1. 1. Alpha Thalassemia By:b.Sadeghi 2008
  2. 2. Alpha thalassemia <ul><li>The thalassemias are the commonest single gene disorders . </li></ul><ul><li>The thalassemias are a hetrogeneous group of genetic disorders of haemoglobin synthesis which result from a reduced rate of production of one or more of the globin chains of haemoglobin. </li></ul><ul><li>Heterozygotes are usually symptomles. </li></ul><ul><li>Clinically are classified according to their severity in to major , minor , intermedia . </li></ul>
  3. 3. Alpha thalassemia <ul><li>Distribution:sub saharan africa,middle east,mediterranean region. </li></ul><ul><li>Genetic disorders of Alpha -chain synthesis result in defective fetal (Hb F) and adult (Hb A) production. </li></ul><ul><li>In fetus:deficiency of Alpha -chains result in production of exess Gama -chains (Hb Bart). </li></ul><ul><li>In adult: deficiency of Alpha -chains result in production of exess Beta -chains (Hb H). </li></ul>
  4. 4. Alpha thalassemia
  5. 5. Molecular pathology <ul><li>α 0-thalassemia : </li></ul><ul><li>Results from deletions of both α -globin genes. </li></ul><ul><li>Result from deletions a bout 40 kb up stream from the α -globin gene cluster. </li></ul><ul><li>α +-thalassemia : </li></ul><ul><li>Results from deletions that remove one of the linked pairs of α -globin genes leaving the other one intact. </li></ul><ul><li>Both α -globin genes are intact but one of them has a mutation that either partially or completely inactivates. </li></ul>
  6. 6. pathophysiology <ul><li>Deficiency of α -chains leads to the production of excess γ or β chains. </li></ul><ul><li>These soluble tetramers ( γ 4 , β 4 )do not percipitate extensively in the bone marrow ,erythropoisis is more effective than in β -thalassemia. </li></ul><ul><li>Hb Bart , Hb H have a very high oxygen affinity. </li></ul>
  7. 7. Hydrops syndrome <ul><li>Follow the homozygous inheritance of α 0 </li></ul><ul><li>thalasemmia. </li></ul><ul><li>There is no production of α -chains(neither fetal nor adult) </li></ul><ul><li>Hb bart :%80 Hb portland:%20 </li></ul><ul><li>This syndrome characterized by: </li></ul><ul><li>Fetal death </li></ul><ul><li>High incidence of toxaemia of pregnancy . </li></ul><ul><li>Obstetric complications( large placenta ) </li></ul>
  8. 8. Hb H disease <ul><li>Most forms due to the coinheritanse of α 0 and α + thalassemia. </li></ul><ul><li>May due to inheritanse of α 0 -thalassemia and Hb constant spring. </li></ul><ul><li>Hb H is unstable and precipitate in red cells. </li></ul><ul><li>Patients usually survive in to adult life. </li></ul><ul><li>Hb H : % 5- % 40 </li></ul><ul><li>Golf body: brilliant cresyl blue . </li></ul>
  9. 9. Alpha thalassemia trait <ul><li>Mild hypochromia anemia. </li></ul><ul><li>Hb A2 is normal. </li></ul><ul><li>Hb Bart :% 5-6 α / β =0.6 </li></ul><ul><li>DNA analysis for certain diagnosis. </li></ul><ul><li>Silent carrier : </li></ul><ul><li>No clinical or hematological abnormality. </li></ul>
  10. 10. ATR - 16 <ul><li>Encoded on chromosom 16 . </li></ul><ul><li>Results from the loss of two megabase from the subtelomereric end of the short arm of chromosom 16. </li></ul><ul><li>Children have a mild degree of mental retardation and no dismorphic feature . </li></ul>
  11. 11. ATR - X <ul><li>Encoded on x chromosom. </li></ul><ul><li>Children have severe mental disorder. </li></ul><ul><li>Results from many diffrent mutations of the ATR X gene. </li></ul>
  12. 12. Molecular diagnosis <ul><li>Almost all method for DNA analysing of the hemoglobinopathies used are based on the PCR . </li></ul>
  13. 13. The PCR based technique used in hemoglobin diagnosis: <ul><li>Allel spesific oligonuclotid (ASO). </li></ul><ul><li>Reverse dot blot analysing. </li></ul><ul><li>Restriction enzyme analysis. </li></ul><ul><li>Amplification refractory mutation system(ARMS) </li></ul><ul><li>Hybridization. </li></ul><ul><li>Gap – PCR. </li></ul>
  14. 14. Other techniques : <ul><li>Direct sequence analysing. </li></ul><ul><li>Suthern blot. </li></ul><ul><li>The α / β globin ratio. </li></ul>
  15. 15. Fetal DNA analysing <ul><li>For prenatal diagnosis. </li></ul><ul><li>Sample( chronic villus in trimester pregnancy). </li></ul><ul><li>PCR thechniques </li></ul>