Paving the Way for Prevention of Haemoglobinopathies in Egypt - Ghada El-Kamah
•
1 like•358 views
An overview of the health system response to haemoglobinopathies in Egypt
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Paving the Way for Prevention of Haemoglobinopathies in Egypt - Ghada El-Kamah
Similar to Paving the Way for Prevention of Haemoglobinopathies in Egypt - Ghada El-Kamah (20)
More from Human Variome Project
More from Human Variome Project (20)
Recently uploaded
Recently uploaded (20)
Paving the Way for Prevention of Haemoglobinopathies in Egypt - Ghada El-Kamah
- 1. The 6th Biennial Meeting of the Human Variome Project Consortium Global Globin 2020 Paving the Way for Prevention of Hemoglobinopathies in Egypt Paris, 30 May-3 June 2016 Ghada El-Kamah, Prof. Clinical Genetics, Coordinator HBD Clinic & Team.
- 2. • Hereditary blood disorders (HBD) are chronic genetic disorders where the affected person suffers ill health all through his life 2 •They have a strong socioeconomic and emotional burden on the governmental and family levels
- 4. The fall in thalassemia major birth rate through several national thalassemia prevention programs THALASSEMI
- 5. • PREVENTION 5 PRENATAL DIAGNOSIS CONVENTIONAL COUNSELING Life long intervention that is sometimes in itself harmful Limitation of availabilities of therapy
- 6. Mild Moderate Severe Age of onset > 6yrs 2-6 yrs < 2yrs Hb level (g/dl) > 8 5-8 < 5 Splenomegaly (cm) 2-4 4-10 >10 +±NoGrowth retardation +±No Facial ± skeletal changes ±±NoSplenectomy >126-12OccasionalTransfusion rate /yr < 3yrs3-6 yrs> 6yrs Age of first transfusion
- 7. 7
- 8. Mutation Our study IVSI,6 26% IVSI,1 18,8% IVSI,110 15,9% IVSII,745 4,57% COD 27 4% IVSII,1 3,9% IVSII,848 3,57% COD 39 2,78% COD 5 2,58% IVSI,5 1,19% COD 28 1,19% Codon 44 0,99% -87 0,99% COD 4 0,39% -29 0,39% COD 9 0,39% COD 37 0,19% COD 15 0,19% -101 0,19% COD 3 0,19% -31 0,19% HbC 0,19% Hb knossoss 0,4%
- 9. Egypt Lebanon Gaza Strip
- 11. 11 Allele frequency 1st fragment 2nd fragment 3rd fragment 4th fragment 5th fragment 6th fragment 7th fragment _ 56% 65% 83% 76% 49% 41% 41% + 44% 35% 17% 24% 51% 59% 59% Allele frequency 1st fragment 2nd fragment 3rd fragment 4th fragment 5th fragment 6th fragment 7th fragment _ 53% 63% 79% 98% 34% 43% 54% + 47% 37% 21% 2% 66% 57% 46% Haplotype of 100 beta-thalassemia cases Haplotype of 100 controls
- 12. Mutation Haplotypes IVS 1.6 (- + + - - - -) 25% (- + - - - + +) 23.3% (+ - - - + - + )11.7% (40% several different haplotypes) IVSI.110 (+ - - - - + + ) 50% (+ - - - -+ - )25% (- - - - - - - )25% IVSI.I (+ - - - - + - )16.6% (- + + - - ++ ) 11.11% (- - - - + + +) 11.11% (the rest were linked to several haplotypes) IVSII.745 (+ - - - - - + ) 50% (+ - - - - + - ) 25% (- + - - - - +) 25% Codon 6 (+ - - - + + + ) 50% (- + - - + + + )25% (- - - - - + - ) 25%
- 17. LCR A wide array of abnormalities, underlie different phenotypes and help in their identification ß-globin locus
- 18. Comparison between the clinical outcomes among different globin gene mutations was performed to evaluate the predictive power of genetic determinants on the phenotypic severity of patients with beta- thalassemia.
- 19. Difference in phenotypes corresponding to ß++/ ß ++ genotype 23.5% 52.9% 23.5% mild severe
- 20. Difference in phenotype corresponding to ß0/ ß0 genotype 12 24 64 mild moderate severe
- 21. This confusion required the studying of genetic modifiers
- 22. group Beta globin mutation Alpha-globin mutation XmnI polymorph severe Late onset Thal. intermedia I ß++/ ß ++ IVSI,6/IVSI,6 IVSI,6/IVSI,6 (10 cases) IVSI,6/IVSI,6 (2cases) -87/-87 IVSI,6/-87 -α3.7/-α3.7 αα/αα unchar. αα/αα αα/αα -/- -/- -/- -/- -/- 0 0 0 0 0 0 0 0 0 0 1 10 2 1 1 II ß++/ ß + IVSI,6/IVSI,110 IVSI,6/IVSI,110 (9 cases) IVSI,6/IVSI,110 IVSI,6/IVSI,110 Unchar. αα/αα -α3.7/-α3.7 -α3.7/αα -/- -/- +/- -/- 1 6 0 0 0 0 0 0 0 3 1 1 III ß+/ ß + IVSI,110/IVSI,110 (7cases) IVSI,110/IVSI,110 IVSI,110/IVSII,745 IVSII,848/IVSII,848 (3cases) IVSI,110/IVSII,848 IVSI,110/IVSII,848 αα/αα -α3.7/-α 3.7 αα/αα αα/αα αα/ααα anti 3.7 αα/αα -/- -/- -/- -/- -/- -/- 4 1 0 0 1 0 1 0 1 1 0 0 2 0 0 2 0 1 IV ß0/ ß 0 IVSI,1/IVSI,1 (7cases) COD5/COD5 COD39/COD39 (2cases) αα/αα αα/αα αα/αα -/- -/- -/- 7 1 1 0 0 0 0 0 1 V ß0/ ß ++ IVSI,6/IVSI,1 Unchar. +/- 1 0 0
- 23. • Thus facing the challenge of prenatal diagnosis • A new study comparing phenotypes among family members carrying the same mutations was conducted
- 24. Family No. proband consang No. of affected members genotype Phenotypic score 1 M +ve 3 ß 0/ ß 0 Severe Severe Severe 2 M +ve 2 ß ++ /ß ++ Moderate Moderate 3 M -ve 2 ß 0/? Moderate Moderate 4 F +ve 2 ß ++/? Mild Mild 5 M -ve 2 ß 0/ ß 0 Moderate Moderate 6 M +ve 2 ß ++ /ß + Severe Severe 7 M +ve 2 ß 0/ ß 0 Severe Severe 8 M +ve 2 ß ++ /ß ++ Moderate Moderate 9 M +ve 3 ß +/ ß + Severe Severe Severe Mild Genotype/phenotype among 20 Betathalassemia families
- 25. Genotype/phenotype among 20 Betathalassemia families (cont) 11 F -ve 2 ß +/ ß + Moderate Moderate 12 M +ve 3 ß +/ ß + Moderate Moderate Moderate 13 F -ve 2 ß 0/ ß + Moderate Moderate 14 F -ve 3 ß +/ ß + Moderate Moderate Moderate 15 M +ve 2 ?/? Moderate Moderate 16 M +ve 2 ß 0/ ß 0 Severe Severe 17 F -ve 2 ß +/ ß 0 Severe Severe 18 M +ve 2 ß +/ ß + Severe Severe 19 F +ve 2 ß +/ ß + Severe Severe 20 F -ve 3 ß 0/ ß 0 Severe Severe Severe
- 26. Other services includes - Introduction of video counseling - Simplified book for the patients and family members - Booklets for the general practitioners about the genetic background of beta thalassemia - Participating in a book about beta- thalassemia
- 27. Parameters Health subjects (n=20) β-thalassemia patients (n=56) P value Median Range (min-max) Median Range (min-max) Neoptrin (mmol/L) 9 6.0-12.8 19 10.0-33.0 0.000* IL-4 (pg/ml) 25,5 8.0-59.0 18 9.0-80.0 0,439 IL-6 (pg/ml) 40,5 25.0-72.0 51,5 21.0-120.0 0.033* hs-CRP (mg/L) 3,6 3.6-4.4 4,2 3.6-14.0 0.005* TNF-α (pg/mL) 37,5 16.0-70.0 49,5 28.0-100.0 0.004* IgA (g/L) 1,7 0.9-2.4 2,3 0.7-5.7 0.004* IgM (g/L) 1,1 0.6-1.8 1,2 0.6-2.5 0,372 IgG (g/L) 10,1 7.2-12.0 14,5 6.0-20.0 0.000* IgG1 (g/L) 6.400 5,100-7,900 9.300 2,614-10,900 0.000* IgG2 (g/L) 4.750 3,000-5,500 5.450 2,500-6,600 0.033* IgG3 (g/L) 470 146.0-1,320.0 879 143.0-1,950.0 0.000* IgG4 (g/L) 137 58.0-380.0 249,5 58.0-815.0 *Statistically significant (p<0.05) IL-4: Interleukin-4, IL-6: Interleukin-6, TNF-α: Tumor necrosis factor-alpha, hs-CRP: High sensitive C-reactive may be due to inflammation which occurs with frequent blood transfusion and is associated with elevation in hs-CRP, the cytokines IL-6 and TNF-α and the immunoglobulins IgA, IgG and subclasses of IgG. This elevation of neopterin was not affected by sex or age Comparison of serum parameters between patients with β-thalassemia and healthy subjects.
- 29. Correlation between physical role and different characteristics Patient's characteristics p-value Gender 0,345 Age 0,354 Blood transfusion 0.004* Origin (urban, rural) 0,77 Mother's educational level 0.000* *statistically significant results ≤ 0.05.. Correlation between emotional role and different characteristics Patient's characteristics p-value Gender 0,239 Age 0,343 Blood transfusion 0,276 Origin (urban, rural) 0,142 Mother's educational level 0.006* *statistically significant results ≤ 0.05. The correla:on of the QoL scores with demographic, clinical and social characteris:cs
- 30. Mean scores of participants for the 8 indicies of the SF-36 test Indicies of SF-36 test Mean scores of NTD patients (SI) Mean scores of TD patients (SD) t-test P-value Physical functioning 70.41 (22.12) 47.44 (22.15) 0.000* Physical role 63.61 (34.77) 28.76 (35.92) 0.000* Emotional role 62.29 (34.28) 60.69 (41.74) 0,87 Vitality 52.32 (22.34) 38.75 (18.41) 0.01* well being 66.85 (12.52) 63.33 (16.07) 0,34 Social functioning 71.30 (22.90) 60.26 (20.99) 0.049* Pain 68.14 (24.51) 61.08 (24.57) 0,258 General health 55.98 (26.36) 41.72 (22.77) 0.024* * Statistically significant The total score of these 8 categories ranges between 0 and 100, with designa.ons of weak (< 20), bad (21-40), good (41-60), very good (61-80), and excellent (> 81) (Montazert et al., 2005). Analysis of data was performed using SPSS 18 for Windows.
- 31. 2158 Three Dimensional Speckle Tracking Echocardiography (3D-STE) for Early Detection of Subtle Myocardial Deformation Dysfunction in Thalassemic Patients Thalassemia and Globin Gene Regulation Program: Oral and Poster Abstracts Session: 112. Thalassemia and Globin Gene Regulation: Poster II Sunday, December 6, 2015, 6:00 PM-8:00 PM Hall A, Level 2 (Orange County Convention Center) In asymptomatic thalassemia patients with preserved left ventricular global systolic function 3D-STE derived strain can detect early subtle myocardial dysfunction. The observed subtle myocardial deformation dysfunction is not related to the extent of myocardial iron deposition.
- 32. 32 Ten families with Sickle Cell Anemia mutation in codon 6 (A>T) HbS. Two patients with sickle-beta thalassemia are found to be having compound heterozygous mutation in two different alleles (Codon6/ IVSI.6) and (Codon6/ IVSII.745). Two amniotic fluid (AF) samples from 2 pregnant mothers with previous sickle cell anemia sibs, revealed heterozygous (A>T) mutation in codon 6 in both cases. Carrier detection was offered in families with positive family history enabling for proper genetic counseling. Sickle Cell Anemia
- 33. Gender Age of onset Hb HBS% Rate of transfusion M 7m 3gm/dl 25 /2 weeks M 16m 4gm/dl 40 once at onset & another at age of 2yrs F S/B 27m 6.8gm/dl 72 never
- 34. Glucose 6 phosphate dehydrogenase deficiency G6PD deficiency is the most common enzyme disorder in humans. It is prevalent in the Mediterranean region, the Middle East, Africa, and South Asia. G6PD deficiency causes neonatal hyperbillirubinemia, acute hemolytic anaemia and in severe cases fatal chronic non-spherocytic haemolytic anaemia. Although X-linked diseases are usually thought to affect males only, homozygous females represent 10% G6PD deficient population. About 10% heterozygous females are G6PD deficient probably due to X-chromosome inactivation.
- 35. 35 Within about 130 million births/year, about 4.5 million newborns are at risk of neonatal jaundice and acute hemolytic crisis. Area % Deficiency Year Study Cairo 42% of males 2013 El-Deen et al. Different urban & rural areas 14.4% 21.2% of males 2010 Abdel Fattah et al. Mansoura 11.4 2006 Settin et al. Tanta (Delta) 12 1996 Hosini et al. (from Settin et al., 2006) Middle Delta 11 1992 Shebl et al. (from Settin et al., 2006) Alexandria 9.8 1986 Hammad et al. (from Settin et al., 2006) In Egypt G6PD among Jaundiced neonates
- 36. 36 Misleading Enzyme assay during hemolytic attacks & missed neonatal cases necessitate further analysis PhD thesis in 2014, through RFLP analysis including 50 cases two Mediterranean mutations were detected in 32% Molecular investigation was performed for 24 families (28 cases). Mediterranean variant 563CT transition represented 35.7 % only i.e. 10 patients, 5 of which were heterozygous females, and the other five were 3 hemizygous males and two homozygous
- 39. Therapeutic options for HBD are limited and it is much more important to control further spread of the disease-causing gene by screening when tests are available.
- 40. Pilot study for screening for β-thalassemia in Egypt: LC MS/MS spectrometry as a cost effective method. Genetic Modifiers in Beta-Thalassemia & Hemophilia-A: A Possible Cause for Altered Therapy. Optimization of use of nanoparticles biosensors as an innovative diagnostic method of HBD.
- 41. 41 Mohamad Ghandour Heba Ahmad Ghada El-Kamah Maha Eid Dalia Abdeen Khalda Amr Eman Bayoumy Rabab Khairat Eman Rabee Noha El Taweel Khaled Gaber Mona Kamal Ahmad Ibrahim Rehab Mosaad abeer Ramadan Naglaa Kholousy Iman Helwa Assem Metwaly Hanan Afiffi Manal Michelle Collaborators NRC STDF Phoebe
- 42. Thank You