CME THALASEMIA 2025 Presentation Latest.

Thalasemia

1. 7 th February 2025 Dr Ahmad Haziq

2. CONTENTS

3. •Thalassaemia is the most common single gene disorder •The disease initially predominant in the Mediteraneans, Southeast Asia •In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. OVERVIEW

4. Source: FARTR 2020

5. Source: FARTR 2020 OVERVIEW

6. OVERVIEW

7. 25% 50% 25% OVERVIEW

8. INCREASE RISK of getting child with Thalassaemia OVERVIEW

9. •Public health concern High cost of treatment. In 2020, there were 8767 thalassemia patients in the registry compared to 4541 patients in 2009 •Affecting mostly Malay & Chinese population & small percentage of Indians. •Sabah has the highest number of Thalassemia patient, Kadazan has the highest prevalence •Estimated 1 in every 20 or 5% carrier amongst Malaysian population OVERVIEW

10. Average life-expectancy: 17 years in 1970 27 years in 1980 37 years in 1990 Since 2000 over 80% of patients have a life expectancy of more than 40 years. OVERVIEW

11. OVERVIEW

12. … The disorder results in large numbers of red blood cells being destroyed, which leads to anemia. DELETION MUTATION PATHOGENESIS

13. PATHOGENESIS

14. A B C D E CLINICAL FEATURES

15. Lifetime cost of TDT patients is estimated to be USD 606,665 = RM 2,858,605.48 CLINICAL FEATURES

16. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Pengenalan - Fakta Seorang individu normal mempunyai 2 gen beta pada kromosom 11 dan 4 gen alpha pada kromosom 16 Seorang individu pembawa gen beta thalassaemia boleh juga membawa gen alpha talasemia

17. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Phenotype Talasemia

18. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Genotype Alpha Talasemia = (α α / α α) Normal α (2 α gene deletion) = (- - / α α) = (- α/ α α) Alpha non- deletional (α T ) = (α T α / α α) e.g. Constant Spring and Adana e.g : Hb Adana = Codon 59 (GGC>GAC) = α CD59 e.g : Hb Constant Spring = Codon 142 (TAA>CAA) = α CS Terminologi G en A lpha α + (1 α gene deletion)

19. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Genotype Beta Talasemia = (β β) Normal = (β E β o ) Pesakit HbE Beta Talasemia Beta Talasemia Trait = (β β) Terminologi Gen Beta Pesakit Beta Talasemia Major = (β β ) HbE heterozygous / trait = (β E β) HbE homozygous = (β E β E )

20. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Jenis-jenis Penyakit Talasemia Penyakit talasemia di Malaysia ( common & clinically significant) Beta talasemia major (β β ) Hb E Beta talasemia (β E β ) Hb H disease ( - - / - α) Hb H- Constant Spring ( - - / α CS α) Hb Barts hydrops fetalis ( - - / - - ) Beta talasemia Alpha talasemia

21. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Jenis-jenis Penyakit Talasemia Penyakit Hb H (Alpha talasemia intermedia) Deletional (- - / - α): Hb H *Non-deletional (- - / α T α): Hb H- Constant Spring * Hb H phenotype Compound heterozygous Hb CS with Hb Adana ( i.e : α CS α / α Adana α) Compound heterozygous Hb CS or Hb Adana with   ( ie : - α / α Adana α ) Homozygous Hb CS or Homozygous Hb Adana ( i.e : α CS α / α CS α ) 3 α genes affected 2 α genes affected * HbH non- deletional is MORE SEVERE than HbH deletional and may cause early abortion (incompatible with life)

22. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Risiko Mendapat Anak Talasemia

23. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Pembawa Gen Talasemia Beta  Beta Talasemia Major Pembawa BetaTalasemia Normal ( homozugous beta zero) (heterozygous beta zero) Ibu ( pembawa ) Bapa ( pembawa ) x 25% 25% 50%  o  o  o  o   o   o   

24. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Pembawa Hb E dan Pembawa Beta  Hb E Beta Thalassaemia (compound heterozygous Hb E Beta) Ibu ( Pembawa Hb E) Bapa ( Pembawa Beta Talasemia ) x 25% 25% 25%  E  o  E  E   o 25% Pembawa Hb E (heterozygous Hb E) Normal Pembawa Beta Thalassaemia (heterozygous Beta) * Thalassaemia Intermedia * Trait = Pembawa   o    * Trait = Pembawa

25. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Kedua-dua Pembawa Alpha Zero ( α o ) - -   - -   - -   - -   - -   - -   Hydrops Fetalis Pembawa  Pembawa  Normal Ibu ( pembawa  ) B apa ( pembawa  ) x 25% 25% 50% - -   - - - -  

26. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Pembawa Alpha Zero ( α o ) dan Pembawa Alpha Plus ( α + ) - -   -    -    - -   - -   -    Ibu (heterozygous  ) x 25% 25% 25% Bapa (heterozygous α + ) Normal HbH Disease (Compound heterozygous  ) Heterozygous α + Heterozygous  25% - -     -    - -   - -   -   

27. MODUL KAUNSELING TALASEMIA MODUL 12 – KAUNSELING GENETIK Pembawa Alpha Zero ( α o ) dan Pembawa Alpha Constant Spring ( α cs )   - -       Ibu (heterozygous α ) x 25% 25% Bapa (heterozygous  CS ) Normal HbH Disease (Non deletional ) Heterozygous α Heterozygous Hb CS 25% 25%  CS    - -    CS  - -  CS 

28. MODUL KAUNSELING TALASEMIA MATRIKS RISIKO Pasangan α trait α + trait α T trait Bukan pembawa α ( telah menjalani ujian DNA alpha globin ) Hb E trait β trait α trait 50% α trait 25% hydrop fetalis 25% bukan pembawa α 25% bukan pembawa α  25% Hb H disease 25% α trait 25% α + trait 25% bukan pembawa α  25% Hb H disease 25% α trait 25% α t trait 50% α trait 50% bukan pembawa α     25% Hb E trait dan α trait 25% α trait 25% Hb E trait 25% normal 25% α trait dan β trait 25% α trait 25% β trait 25% normal α + trait   50% α + trait 25% α + homozygous 25% bukan pembawa α  25 % α T trait 25% α + trait 25% α + / α T compound heterogygous 25% bukan pembawa α  50% α + trait 50% bukan pembawa α     25% Hb E trait dan α + trait 25% α + trait 25% Hb E trait 25% bukan pembawa α 25% α + trait dan β trait 25% α + trait 25% β trait 25% bukan pembawa α α T trait     50%α T trait 25% α T homozygous 25% bukan pembawa α 50% α + trait 50% bukan pembawa α     25% Hb E trait dan α T trait 25% α T trait 25% Hb E trait 25% bukan pembawa 25% α T trait dan β trait 25% α T trait 25% β trait 25% bukan pembawa Bukan pembawa α ( telah menjalani ujian DNA alpha globin)       100% bukan pembawa α  50% Hb E trait 50% bukan pembawa α 50% β trait 50% bukan pembawa α Hb E trait         50% Hb E trait 25% Hb E homozygous 25% bukan pembawa 25% Hb E β thal . 25% Hb E trait 25% β trait 25% bukan pembawa β trait           50% β trait 25% β thal . major 25% bukan pembawa Risiko mendapat anak Talasemia Status Saringan Talasemia Bapa Status Saringan Talasemia Ibu

29. MODUL KAUNSELING TALASEMIA Clinical significance of :   Gene / genes affected Patient / Carrier Symptoms Hb H disease 3 α genes affected Patient Moderate anaemia and usually not transfusion dependent Hb H phenotype 2 α genes affected at both allele Patient Moderate anaemia and usually not transfusion dependent α trait (heterozygous) 2 α genes affected Carrier Asymptomatic (FBC parameters are more severe) α o homozygous 2 α genes affected at both allele α Thal major Hydrops foetalis α + trait (heterozygous) 1 α gene affected Carrier Asymptomatic α + homozygous 1 α gene affected at both allele Carrier Asymptomatic Hb E trait 1 β gene affected Carrier Asymptomatic Hb E homozygous β genes affected at both allele Carrier Asymptomatic Hb E trait with α trait 1 β gene with concomitant 2 α genes affected Carrier Asymptomatic Hb E trait with α + trait 1 β gene with concomitant 1 α gene affected Carrier Asymptomatic Hb E β Thalassaemia 2 β genes affected Patient Moderate to severe anaemia β trait 1 β gene affected Carrier Asymptomatic α trait with β trait 2 α genes with concomitant 1 β gene affected Carrier Asymptomatic α + trait with β trait 1 α gene with concomitant 1 β gene affected Carrier Asymptomatic

30. Hematology analyzer for fbc test INVESTIGATIONS & DIAGNOSIS FBC - CONVERTED TO HB ANALYSIS SARINGAN TALASEMIA TING 4 NAMA, I/C 12 DIGIT, SEX, RACE, NAMA KK/UPKS LENGKAP Cop nama , & tandatangan Pegawai perubatan Hb Analysis (for beta thala or HbE trait only) High performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE)

31. INVESTIGATIONS & DIAGNOSIS Hb normal, MCH > 27 : not thalassemia carrier Hb normal, MCH ≤ 27 : TRO thalassemia trait Hb low, MCH ≤ 27 : TRO IDA Hb low, MCH > 27 : Others (? Folate/B12 def.) Mentzer’s index (IDA VS Beta thala trait) CPG does not recommend it as it has contradictory upon its accuracy

32. INVESTIGATIONS & DIAGNOSIS DNA ANALYSIS May proceed with this test based on Hb Analysis result Useful to diagnose alpha & beta thalassemia traits or other hemoglobinopathies Takes about 3-6 months for the result Only available in HKL, HSB Kedah and IMR

33. INVESTIGATIONS & DIAGNOSIS Hb Analysis & DNA Analysis code

34. MANAGEMENT

35. MANAGEMENT

36. Thalassemia Carrier in Pregnancy