Pandiarajan Vignesh1, Amit Rawat1, Rajni Kumrah1, Ankita Singh1, Anjani Gummadi1, Madhubala Sharma1, Anit Kaur1, Johnson Nameirakpam1, Ankur Jindal1, Deepti Suri1, Anju Gupta1, Alka Khadwal2, Biman Saikia3, Ranjana Walker Minz3, Kaushal Sharma1, Mukesh Desai4, Prasad Taur4, Vijaya Gowri4, Ambreen Pandrowala5, Aparna Dalvi6, Neha Jodhawat6, Priyanka Kambli6, Manisha Rajan Madkaikar6, Sagar Bhattad7, Stalin Ramprakash8, Raghuram Cp8, Ananthvikas Jayaram9, Meena Sivasankaran10, Deenadayalan Munirathnam10, Sarath Balaji11, Aruna Rajendran11, Amita Aggarwal12, Komal Singh12, Fouzia Na13, Biju George13, Ankit Mehta14, Harsha Prasada Lashkari15, Ramya Uppuluri16, Revathi Raj16, Sandip Bartakke17, Kirti Gupta18, Sreejesh Sreedharanunni19, Yumi Ogura20, Tamaki Kato20, Kohsuke Imai20,21, Koon Wing Chan22, Daniel Leung22, Osamu Ohara23, Shigeaki Nonoyama20, Michael Hershfield24, Yu-Lung Lau22, Surjit Singh1. 1. Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 2. Bone Marrow Transplantation Unit, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 3. Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 4. Department of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India. 5. Bone Marrow Transplantation Unit, Bai Jerbai Wadia Hospital for Children, Mumbai, India. 6. ICMR-National Institute of Immunohematology, Mumbai, India. 7. Pediatric Immunology and Rheumatology, Aster CMI hospital, Bengaluru, India. 8. Pediatric Hemat-oncology and BMT Unit, Aster CMI Hospital, Bengaluru, India. 9. Anand Neuberg Diagnostic and Research Centre, Bengaluru, India. 10. Kanchi Kamakoti Child Trust Hospitals for Children, Chennai, India. 11. Institute of Child Health, Madras Medical College, Chennai, India. 12. Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. 13. Christian Medical College, Vellore, India. 14. Zydus Hospitals, Ahmedabad, India. 15. Department of Pediatrics, Kasturba Medical College, Mangalore, India. 16. Apollo Children's Hospital, Chennai, India. 17. Aditya Birla Memorial Hospital, Pune, India. 18. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 19. Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 20. Department of Pediatrics, National Defense Medical College, Saitama, Japan. 21. Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 22. Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong. 23. Kazusa DNA Research Institute, Chiba, Japan. 24. Duke University Medical Center, Durham, NC, United States.
Abstract
Background: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce. Objective: To describe clinical and laboratory features of SCID diagnosed at immunology centers across India. Methods: A detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID. Results: We obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%). Conclusion: We document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.
Background: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce. Objective: To describe clinical and laboratory features of SCID diagnosed at immunology centers across India. Methods: A detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID. Results: We obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%). Conclusion: We document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.
Authors: M Noguchi; H Yi; H M Rosenblatt; A H Filipovich; S Adelstein; W S Modi; O W McBride; W J Leonard Journal: Cell Date: 1993-04-09 Impact factor: 41.582
Authors: M Vihinen; F X Arredondo-Vega; J L Casanova; A Etzioni; S Giliani; L Hammarström; M S Hershfield; P G Heyworth; A P Hsu; A Lähdesmäki; I Lappalainen; L D Notarangelo; J M Puck; W Reith; D Roos; R F Schumacher; K Schwarz; P Vezzoni; A Villa; J Väliaho; C I Smith Journal: Adv Genet Date: 2001 Impact factor: 1.944
Authors: Fiona Poyer; Raúl Jimenez Heredia; Wolfgang Novak; Petra Zeitlhofer; Karin Nebral; Michael N Dworzak; Oskar A Haas; Kaan Boztug; Leo Kager Journal: Front Immunol Date: 2022-06-24 Impact factor: 8.786
Authors: Koon-Wing Chan; Chung-Yin Wong; Daniel Leung; Xingtian Yang; Susanna F S Fok; Priscilla H S Mak; Lei Yao; Wen Ma; Huawei Mao; Xiaodong Zhao; Weiling Liang; Surjit Singh; Mohamed-Ridha Barbouche; Jian-Xin He; Li-Ping Jiang; Woei-Kang Liew; Minh Huong Thi Le; Dina Muktiarti; Fatima Johanna Santos-Ocampo; Reda Djidjik; Brahim Belaid; Intan Hakimah Ismail; Amir Hamzah Abdul Latiff; Way Seah Lee; Tong-Xin Chen; Jinrong Liu; Runming Jin; Xiaochuan Wang; Yin Hsiu Chien; Hsin-Hui Yu; Dinesh Raj; Revathi Raj; Jenifer Vaughan; Michael Urban; Sylvia van den Berg; Brian Eley; Anselm Chi-Wai Lee; Mas Suhaila Isa; Elizabeth Y Ang; Bee Wah Lee; Allen Eng Juh Yeoh; Lynette P Shek; Nguyen Ngoc Quynh Le; Van Anh Thi Nguyen; Anh Phan Nguyen Lien; Regina D Capulong; Joanne Michelle Mallillin; Jose Carlo Miguel M Villanueva; Karol Anne B Camonayan; Michelle De Vera; Roxanne J Casis-Hao; Rommel Crisenio M Lobo; Ruby Foronda; Vicky Wee Eng Binas; Soraya Boushaki; Nadia Kechout; Gun Phongsamart; Siriporn Wongwaree; Chamnanrua Jiratchaya; Mongkol Lao-Araya; Muthita Trakultivakorn; Narissara Suratannon; Orathai Jirapongsananuruk; Teerapol Chantveerawong; Wasu Kamchaisatian; Lee Lee Chan; Mia Tuang Koh; Ke Juin Wong; Siew Moy Fong; Meow-Keong Thong; Zarina Abdul Latiff; Lokman Mohd Noh; Rajiva de Silva; Zineb Jouhadi; Khulood Al-Saad; Pandiarajan Vignesh; Ankur Kumar Jindal; Amit Rawat; Anju Gupta; Deepti Suri; Jing Yang; Elaine Yuen-Ling Au; Janette Siu-Yin Kwok; Siu-Yuen Chan; Wayland Yuk-Fun Hui; Gilbert T Chua; Jaime Rosa Duque; Kai-Ning Cheong; Patrick Chun Yin Chong; Marco Hok Kung Ho; Tsz-Leung Lee; Wilfred Hing-Sang Wong; Wanling Yang; Pamela P Lee; Wenwei Tu; Xi-Qiang Yang; Yu Lung Lau Journal: Front Immunol Date: 2022-07-08 Impact factor: 8.786