Dr. Maryam Mohd. Fatma Matar, Founder & Chairperson, UAE Genetic Diseases Association

1. Cost Effectiveness of Population Screening Program in UAE • Premarital Screening & Improving the quality of genes • Neonatal Screening • Manal Campaign Dr. Maryam Mohd. Fatma Matar, Founder & Chairperson, UAE Genetic Diseases Association

2. UAE Genetic Diseases Association (UAEGDA) and Sheikh Zayed Research Centre were founded in 2004 as a dedication to the memory of His Highness Sheikh Zayed bin Sultan Al Nahyan, founding father of the U.A.E. We renew our pledge to serve the community in 2018, the “Year of Zayed.”

3. UAE Genetic Diseases Association Vision Pioneer in preventive program for common genetic disorders in UAE and the region. Mission Strive to reduce the prevalence and impact of common genetic disorders in the UAE through preventative awareness programs, screening based on research studies and knowledge sharing, conducted by experts in the field using the most innovative and cost effective technology.

4. UAE GDA Objectives • Increase awareness of the common genetic disorders in the UAE and the region • Empowering the community with reliable, credible and easy-to-use information about the common genetic disorders, especially preventable disorders and share the tools and services which are: • Available • Affordable • Accessible • Promote “Women in STEM” through action-led and sustained programs and initiatives • Establish comprehensive proposals on new findings which support/recommend • A) New Legislations • B) Human Resources Requirements • C) Education curriculum across the nation. • Establish a reference database of genetic disorders on evidence based research conducted in collaboration with our regional and international research partners.

5. HH Sheikh Nahyan Bin Mubarak Al Nahyan Our Patron • Cabinet Member and Minister of State for Tolerance of UAE • President, UAE Genetic Diseases Association ` The core volunteer team in year 2005

6. His Highness Sheikh Mohammed bin Rashid Al Maktoum Vice President and Prime Minister of the United Arab Emirates and ruler of Dubai inaugurated Sheikh Zayed Research Centre in 2007

7. UAE GDA Milestones Pioneering the advocacy and awareness on genetic screening which led to: • Mandatory Premarital screening legislation in the UAE • Mandatory newborn screening legislation in the UAE • A national screening program for the common genetic blood disorders in 2006 aimed at identifying Thalassemia, Sickle cell anemia and G6PDH carriers in the UAE population. • Manal – Folic Acid prevention program & WHO fortified wheat campaign • A recent cabinet decision that rules that unmarried women and couples can now freeze their eggs in the UAE. • Legislation on ban of smoking in public places in UAE

8. UAE GDA Milestones 2003-2004 2005 2007 2001 • Community Outreach Program - Blood Screening for genetic disorders 1114 students at Latifa Hospital UAE Free of Newly Born Children with Thalassemia Campaign Legislation of premarital screening made mandatary • Official Inauguration of • Sheikh Zayed Research Centre • by H.H. Sheikh Mohammed bin Rashid Al Maktoum • Introduced popular screening program for Hemoglobinopathies

9. UAE GDA Milestones 2009 2010 2011 Launched the 1st edition of annual International Genetic Conference Arabic Magazine on Genetics - Nawah Folic Acid Deficiency Campaign

10. UAE GDA Milestones 2016 2012 2017 • 6th Annual International Genetic Conference & Awards • RARE Rare Diseases Society • Rare Diseases Excellence Awards • GCC Genomics Society • Partnership with Saudi Genome Project • Launch of Alzheimer support group • Familial Hypercholesterolemia Project • Vitamin D deficiency campaign • Fragile X Chromosome Project • Non-communicable Diseases Alliance . • Noble Laureates visit • UAE GDA • Ebtisam Society and support group for cancer survivors

11. Noble laureates Support UAE GDA In 2012, UAE GDA received a massive vote of support from Noble Laureates who visited our facility. “UAE GDA is a spot of light in Arab world” was the message of these esteemed scientists

13. PREMARITAL SCREENING (PS) Definition: Premarital Screening (PMS) is defined as a panel of tests in which couples that are going to get married are tested for genetic, infectious and blood transmitted diseases to prevent any risk of transmitting any disease to their children. Aim: To Motivate the general populations and revive the interest of stakeholders involved in the management of inherited genetic disorders and thereby proposing and implementing premarital screening programs in UAE at a national level

14. Neonatal screening: Newborn screening tests look for developmental, genetic, and metabolic disorders in the newborn baby. This allows steps to be taken before symptoms develop. Most of these illnesses are very rare, but can be treated if caught early PGD for Inherited diseases: Pre-Implantation Genetic Diagnosis (PGD) allows for the diagnosis of inherited diseases or conditions within an embryo during In Vitro Fertilization (IVF). In the case of PGD for a Single Gene Disorder , embryos are diagnosed with a genetic disorder that may be passed on due to one or both parents carrying an inherited disease

15. Impact Of Premarital Screening In UAE Hemoglobinopathies screening statistics 2007- 2017 Total no. of Cases Screened: 32,849 No. of cases screened positive for Haemoglobinopathies : 16220 No. of cases screened negative for Haemoglobinopathies : 16629

16. Impact of PS- 2007-2017Cases detected and the financial savings • The cost of screening in the government sector is AED1000 in the private sector is more than AED1,800 • Thalassemia cases only according to estimates by the Dubai Health Authority in 2007: Savings per case for = AED35,850 Savings for all cases = AED32,372,550

18. Consequences of Folic Acid Deficiency – Neural Tube Defects Neural Tube Defects like anencephaly and spina bifida In China Folic Acid Community Intervention, the investigators found that among women who took 400 mcg/d of folic acid from the time of their premarital examination until the end of the first trimester of pregnancy, the risk of NTDs was reduced by 85 % in the region with high risk for NTDs and by 40 % in the low risk region

19. Manal Campaign to Manage Neuro-tubal defects Working towards healthier quality of genes • UAE Genetic Diseases Association national campaign for prevention of folic acid deficiency was launched in the Dubai Women's College and thereafter across UAE. • The aim of the national campaign is: • Prevention of folic acid deficiency within the country. • Prevent the massive healthcare costs of managing NTD patients AED 72 = Cost of a 3-month supplement course of Multi-Vitamin Tablet containing four mg Folic Acid AED 3 million = cost of managing one child /patient born with NTD for his/her life-time

20. Cost Impact of prevention of folic acid deficiency vs management of NTD Prevention costs: UAE University students covered under the campaign := 13,875 Cost of Folic Acid Supplement for 3 months: AED 72 Annual cost of supplement campaign = AED 320,000

21. WHY PREMARITAL SCREENING? • To prevent genetic disorders, congenital anomalies & several medical, psychological marital problems. • To examine the detection and prevention of at risk marriages. • E.g.: G6PDH (X-Linked recessive) Salem story

22. Importance of Premarital screening • Designed to create a general infrastructure for prevention of genetic disorders. • This should be available to anyone who want the screening. • Informed consent is necessary, • Guarantees confidentiality. • Educate all members of the screening team (laboratory technologists, nurse practitioners, physicians, counselors, outreach workers and social workers).

23. ROLE OF CULTURE AND EDUCATION  SUCCESS OF PS Consanguinity refers to relationship by blood or common ancestry, in which the chances of inheriting a recessive disease are increased; the closer the relationship the greater the risk. Marriages between same tribes or extended family groups are favored in some cultures, including those between first cousins. PS plays a role in educating families the relevance of genetically transmitted diseases and the possibility of risk reduction.

24. ‘SOLUTION-FOCUSED’ PREMARITAL COUNSELING Role of IVF & Premarital screening Making aware of the genetic makeup Pre-implantation screening based on counseling Reproductive options for those who proceed with the marriage following prenatal diagnosis Adoption of the affected child, donation of sperm, ova or a pre-embryo from an unaffected individual and pre-implantation diagnosis Choosing the best option depends on availability, cost and local regulations and religious rules.

25. Issues related to premarital screening in Arab World • Importance of partnerships with Physicians, Scientists, medical personnel, politicians, intellectuals, religious motivators, teachers, socio-cultural organizations and activists, law and policy makers. • Role to motivate the people about PS testing and formulation of legislation for premarital screening program and implementation it in the country.

26. CONCLUSION PSP is mandatory & can influence marriage decision. Allows informed reproductive decisions Marks up individuals for prenatal diagnosis Ultimate goal is to reduce birth incidence UAE Free of Thalassemia 2012 was achieved in collaboration with the stakeholders and the most important pre-marriage legislation.

28. Premarital screening in various countries

29. Neonatal screening

30. Case study-UAE - Expanding the comprehensive national neonatal screening programme  from 1995 to 2011. The research conducted by the authors reports data since the programme started in January 1995 up to December 2011 on the incidence of screened disorders and the molecular basis of positive screened cases.  Screening used a combination of tandem mass spectrometry, molecular technologies and biochemical analysis. A total of 750 365 infants were screened and 717 babies saved from associated morbidity and/or mortality. The incidence of screened disorders were 1:1 873 for congenital hypothyroidism, 1:14 544 for phenylketonuria, 1:3 526 for amino acid, organic acid and fatty acid disorders, 1:9 030 for classical congenital adrenal hyperplasia, 1:8 300 for biotinidase deficiency, 1:2 384 for sickle-cell disease and 1:121 for sickle-cell traits. Coverage of neonatal screening in the population reached 95% in 2010. Expanding the comprehensive national neonatal screening programme in the United Arab Emirates from 1995 to 2011. Al Hosani H1, Salah M2, Osman HM3, Farag HM2, El-Assiouty L2, Saade D1, Hertecant J4. Author information 1 Central Department of Maternal and Child Health, Ministry of Health, Abu Dhabi, United Arab Emirates. 2 Department of Genetics, National Screening Centre, Abu Dhabi, United Arab Emirates. 3 National Screening Laboratory, National Screening Centre, Abu Dhabi, United Arab Emirates. 4 Department of Paediatrics, Tawam Hospital, Abu Dhabi, United Arab Emirates. https://www.ncbi.nlm.nih.gov/pubmed/24932929

31. Case study-USA- Impact of Neonatal screening - Phenylketonuira (PKU)under Mother Child Health Program Since the inception of screening and coordinated management, over 95% of children with PKU achieve normal or near normal intelligence compared to just 1% prior to screening. https://www.jhsph.edu/research/centers-and-institutes/womens-and-childrens-health-policy-center/publications/Res_Syntheses/NewbornScreening.pdf

32. Case study-China - Impact of Neonatal screening - Glucose 6-phosphate dehydrogenase (G6PD) Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a global disease affecting multi-ethnic populations with red blood cell enzyme defects and hemolytic anemia; more than 4 million patients worldwide suffer from this deficiency. Southeast Asia, the Middle East, and China are prone to this disorder. Around 1,705,569 neonatal subjects were enrolled for the screening from 1989 to 2011 (September) from Guangzhou, China in this study. http://www.funpecrp.com.br/gmr/year2014/vol13-2/pdf/gmr3422.pdf

33. Neonatal screening in UAE • The Newborn Screening Program in the UAE is a Comprehensive Newborn Screening Program which encompass; Parent Education, Comprehensive Newborn Physical Exam, Screening Tests, follow-up, Diagnosis, Counseling, Management and Treatment & Evaluation. • Genetic Disorders test is done for: • Phynylketonuria. Congenital Hypothyroidism Cystic Fibrosis • Congenital Adrenal Hyperplasia Sickle Cell anemia (Hb S/S) and Sickle Cell anemia (Hb S/C) • Thalassemia Galactosemia Biotinidase Hearing Loss • Glucose 6 Phosphate Dehydrogenase Deficiency (G6PD) • These conditions were selected on the basis of assessment of public health needs, potential benefits and cost-effectiveness of early detection and management of newborns diagnosed with these condition(s) and prevention of hazardous complications and improving health outcomes

34. Technology aiding Neonatal screening Cardiff University scientists developed a diagnostic kit in August 2017 to screen for Duchenne muscular dystrophy (DMD) in newborns using dried blood spots. Previous attempts at developing a diagnostic kit using blood spot CK (creatinine kinase) enzyme assays were met with little success Prior tests could not distinguish between the three different forms of CK that are present in muscle tissue, which include CK-MM, CK-MB, and CK-BB. “The successful outcome of this study is an example of the impact that can be achieved through collaboration between academic, clinical and industry colleagues in developing improvements in human healthcare,” Dr. Ian Weeks, Professor at Cardiff University School of Medicine and the lead author of the study

35. Future of Neonatal screening It has been estimated that close to 131 million babies are born each year across the globe. Of these, approximately 7.9 million are born with birth defects. In fact, more than 7,000 genetic disorders have been identified so far and the number is rising. Enter Gene editing tool CRISPR

36. Genome A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus. Almost every cell in your body has a genome. Your genome is your complete set of DNA that makes you unique. Think of it as yourpersonal barcode.

37. How CRISPR works?

38. Challenges, Opportunities and Concerns Testing babies for genetic diseases: Are we ready for next generation screens? As genetic testing techniques become more sensitive and sophisticated, are public health agencies and the medical profession ready for them? This question becomes increasingly important now that more than 60 countries have adopted newborn screening programs and the technology behind screening is starting to shift toward more data-intense next-generation sequencing.

39. REFERENCES • Christine EM. Couples Resource Map Scales study. University of North Carolina (USA). Available at: http://www. couplesresourcemap.org/ (last accessed November 2008) • El-Hamzi MA. Pre-marital examination as a method of prevention from blood genetic disorders. Community views. Saudi Med J 2006; 27(9): 1291-5. • Al Sulaiman A, Sulaiman A, Al Mishari M, Al Sawadi A, Owaidah TM. Knowledge and attitude toward the hemoglobinopathies premarital screening program in Saudi Arabia: Population-based survey. Hemoglobin 2008; 32 (6): 531-8. Al-Gazali L, Hamamy H, Al-Arrayad S. Genetic disorders in the Arab world. BMJ. 2006; 333: 831–834. • Matar M, Naveed M. Internet-based approach to population screening forcommon hemoglobinopathies in United Arab Emirates.Nursing and Health Sciences.2011 • Laurence J,Henderson S,Howitt P, Matar M, Kwari H,Levitan S,Darzi A .Patient Engagement :Four case studies that highlight the potential for improved health outcomes and reduced cost.2014;The people to people health Foundation • http://www.funpecrp.com.br/gmr/year2014/vol13-2/pdf/gmr3422.pdf • https://www.jhsph.edu/research/centers-and-institutes/womens-and-childrens-health-policy-center/publications/Res_Syntheses/NewbornScreening.pdf • https://geneticliteracyproject.org/2016/04/28/testing-babies-genetic-diseases-ready-next-generation-screens/ • https://www.ncbi.nlm.nih.gov/pubmed/28209627 • https://www.ncbi.nlm.nih.gov/pubmed/24932929

40. 9-10 November 2018 www.uaegda.ae Venue: Park Hyatt Dubai

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