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BY: Dr. MOHD SALAH

THALASSEMIA INTERMEDIA. Data from Dubai Thalassemia Centre . BY: Dr. MOHD SALAH. Chromosome 11 -globin gene. Chromosome 16 -globin gene. Chromosomes. INHERETENCE. An example of inheritance: Marriage between two carriers. Red blood cell. Oxygen from lungs.

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BY: Dr. MOHD SALAH

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  1. THALASSEMIA INTERMEDIA Data from Dubai Thalassemia Centre BY: Dr. MOHD SALAH

  2. Chromosome 11 -globin gene Chromosome 16 -globin gene Chromosomes

  3. INHERETENCE An example of inheritance: Marriage between two carriers

  4. Red blood cell Oxygen from lungs Oxygen released to tissue cells Hemoglobin molecules Oxygen boded with hemoglobin molecules

  5. Molecular Basis of Thalassemia Intermedia 1. Homozygous or compound heterozygous state for b thalassemia • Inheritance of mild b thalassemia alleles • Co-inheritance of a thalassemia • Increased Hb F response • Xmn1 –polymorphism • b promoter mutations • Trans-acting HPFH genetic determinants

  6. Molecular Basis of Thal. Int. cont. 2. Heterozygous state for b thalassemia a) Co-inheritance of extra a globin genes (aaaa/aa, aaa/aaa, aaa/aa) b) Dominantly inherited b thalassemia (Hyperunstable b chainvariants) 3. Compound heterozygous for b thalassemia and b chain variants e.g. Hb E 4. Compound heterozygotes for b thalassemia and HPFH .

  7. Aids to Predict Thal. Intermedia Cases • -Thalassaemia genotypes of • parents • HbF values in parents • Co-inheritance of a thalassemia • Age at presentation • Level of Hb at presentation • Level of Hb A

  8. THALASSEMIA INTERMEDIA IN DUBAI

  9. METHODS All patients had: • Serial FBCs • Hb Electrophoresis (HPLC) &/ or IEF • Molecular characterization of alpha genes ( Deletional and non-deletional) • Beta genes mutations &Xmn1 • Clinical monitoring of any possible complication

  10. HAEMOGLOBIN ELECTROPHORESIS&IEF • bo b+ • HbA: Decreased • HbF: Inc(80-90 %) • HbA2: Variable • b+b+ • HbA: Decreased(>20%) • HbF: Inc(70-80 %) • HbA2: N or Increased

  11. RESULTS • The mean age is 11 (3-33) yrs, • Non-deletional alpha-gene mutation was normal in all our patients. • Most of pts have mild to moderate thalassemic features. • Average hemoglobin level : 8.5 g/dl. • 40% of patients had infrequent hemoglobin drop needed blood transfusion.

  12. INCIDENCE 82.52% 8.64% 8.84%

  13. TYPE OF MUTATION

  14. GENDER

  15. SEVERE MUTATIONS =18 • 9 = IVS 1 - 5 (G-C) / IVS 1 - 5 (G-C) • 4 = IVS 1 - 5 (G-C) / - 25 bp del • 3 = IVS 1 - 1(G-C) / IVS 1 – 1(G - C) • 1 = IVS 1 - 1 (G-T) / IVS 1 - 1 (G - T) • 1 = -25 bp del / -25 bp del

  16. MILD MUTATIONS = 13 • 2= CD 26 (G-A) / Milder mutation • 2= IVS 11–1 (G-C) / IVS 11 – 1 • 1= IVS 1-6 (T-C) / IVS 1-6 (T-C) • 1= CD 27 (G-T) / CD 39 (G-T) • 1= CD 26 (G-A) / IVS 1 – 130 (G-C) • 2= VS 1-6 (T-C) / mild • 2= IVS 1-6(T-C) / IVS II-848(C-A) • 2 = Cd 8 (-AA) / Cd 8 (-AA)

  17. SEVERE / MILD = 9 • 2= IVS 1 - 5 (G-C) / - 88 (C-A) • 3= IVS 1 - 5 (G-C) / Poly A • 2= IVS 1– 5 (G-C) / CD 26 (G-A) • 1= IVS 1 – 5 (G-C)/ • 1= -25 bp del / CD 27 (G-T)

  18. MUTATIONS VERSUS SEVERITY

  19. COMMONEST MUTATION IN UAE IVS 1-5(GC) =19

  20. SEVERE MUTATIONS a-Thal. Status 18 severe - mutation 4 heterozygous -thal 3.7 8 normal - thal 6 homozygous -thal 3.7

  21. Mutation Versus frequency of Tx

  22. RARELY TRANSFUSED PTs • 4/20 (20%) patients received blood transfusion rarely • 4/4 (100%) are homozygous positive for XmnI, • 2/4 (50%) are heterozygous for –3.7 alpha-gene mutation (alpha-thalassemia trait)

  23. NEVER TRANSFUSED

  24. 5 PTs never transfused with severe mutations 1-Pt a- Thal. Trait

  25. Reason for Planned Transfusion

  26. B-THAL. INTERMEDIA

  27. PLAIN X-RAYS IN THAL. PTs

  28. CONCLUSION

  29. Among the known factors affecting the phenotypic severity in our pts.: • Type of Beta mutation. • The presence of alpha-gene defect. • XmnI mutation (homozygous and hetero) would ameliorate the clinical course. • Two of our patients have severe mutation with normal a-thal and normal Xmn1 • Further studies still needed to specify other factors.

  30. AKNOWLEDGEMENT Al Wasl Hospital, Genetic and Thalassemia Center, Dubai, UAE. • Erol Baysal, PhD • Aref Chehal, MD • Maisam Bakir,MD • Essam Dohair, MD • Lab. Technicians • Nursing Staff • Abdulla Alkhayat.MD

  31. THANK YOU

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