AUTHOR=Vignesh Pandiarajan , Rawat Amit , Kumrah Rajni , Singh Ankita , Gummadi Anjani , Sharma Madhubala , Kaur Anit , Nameirakpam Johnson , Jindal Ankur , Suri Deepti , Gupta Anju , Khadwal Alka , Saikia Biman , Minz Ranjana Walker , Sharma Kaushal , Desai Mukesh  , Taur Prasad , Gowri Vijaya , Pandrowala Ambreen , Dalvi Aparna , Jodhawat Neha , Kambli Priyanka , Madkaikar Manisha Rajan , Bhattad Sagar , Ramprakash Stalin , CP Raghuram , Jayaram Ananthvikas , Sivasankaran Meena , Munirathnam Deenadayalan , Balaji Sarath , Rajendran Aruna , Aggarwal Amita , Singh Komal , Na Fouzia , George Biju , Mehta Ankit , Lashkari Harsha Prasada , Uppuluri Ramya , Raj Revathi , Bartakke Sandip , Gupta Kirti , Sreedharanunni Sreejesh , Ogura Yumi , Kato Tamaki , Imai Kohsuke , Chan Koon Wing , Leung Daniel , Ohara Osamu , Nonoyama Shigeaki , Hershfield Michael , Lau Yu-Lung , Singh Surjit 

TITLE=Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.619146

DOI=10.3389/fimmu.2020.619146

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Objective</title><p>To describe clinical and laboratory features of SCID diagnosed at immunology centers across India.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 - <italic>IL2RG</italic> (36), <italic>RAG1</italic> (26), <italic>ADA</italic> (19), <italic>RAG2</italic> (17), <italic>JAK3</italic> (15), <italic>DCLRE1C</italic> (13), <italic>IL7RA</italic> (9), <italic>PNP</italic> (3), <italic>RFXAP</italic> (3), <italic>CIITA</italic> (2), <italic>RFXANK</italic> (2), <italic>NHEJ1</italic> (2), <italic>CD3E</italic> (2), <italic>CD3D</italic> (2), <italic>RFX5</italic> (2), <italic>ZAP70</italic> (2), <italic>STK4</italic> (1), <italic>CORO1A</italic> (1), <italic>STIM1</italic> (1), <italic>PRKDC</italic> (1), <italic>AK2</italic> (1), <italic>DOCK2</italic> (1), and <italic>SP100</italic> (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%).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>