SCID pathogenesis involves multiple genes whose defect which leads to abnormal cellular and humoral immune responses. Severe combined immunodeficiency (SCID) refers to a heterogeneous group of primary immunodeficiency disorders characterized by impaired T lymphocyte development with an effect on the B cell and NK cell number and/or function. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL). Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect ( n = 12) followed by IL2RG ( n = 9) and JAK3 defects ( n = 9). A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. MHC class II deficiency accounted for 10.5% of our patient group. Based on immunophenotypic pattern, majority of the cases were T −B − SCID (39%) followed by T −B + SCID (28%). Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Four patients underwent HSCT in our cohort but had a poor survival outcome.
Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Majority of our patients (89%) presented within 6 months of age. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. 11Department of Pediatrics Hematology and Oncology, Indraprastha Apollo Hospital, New Delhi, India.10Department of Pediatrics, Institute of Maternal and Child Health, Government Medical College, Kozhikode, India.9Department of Pediatrics, Sri Ramachandra Medical College and Research Institute, Chennai, India.8Department of Pediatrics, Kasturba Medical College, Mangalore, India.7Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.Hinduja National Hospital & Research Center, Mumbai, India
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