ADVANCEMENTS IN ADA-SCID: A DETAILED COMPILATION WITH DIAGNOSTIC APPROACHES AND PROPOSITIONS OF NOVEL TREATMENT MODALITIES

The aim of the study is to evaluate the prevalence and impact of advancements in the diagnosis and treatment of Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) and propose novel strategies for improved management and therapeutic outcomes. A comprehensive review was conducted according to PRISMA guidelines, focusing on advancements in ADA-SCID. Gene variant data were analysed using databases like dbSNP and ClinVar, with pathogenicity assessed using tools such as SIFT and PolyPhen. The methodology includes a comprehensive review of studies from 1970–2024 was performed, emphasizing diagnostics (e.g., TREC screening, genomic sequencing) and therapies (e.g., enzyme replacement therapy, HSCT, and gene therapy). The study highlighted the pathogenic variants of the ADA gene contributing to ADA-SCID, diagnostic challenges, and the associated vaccination risks. Current therapeutic approaches, including enzyme replacement therapy, hematopoietic stem cell transplantation, and gene therapy, were reviewed, emphasizing their benefits and limitations. Novel therapies, such as CRISPR-Cas9 base editing, in-utero stem cell transplantation, and iPSC-derived treatments, demonstrated promising potential for future management of ADA-SCID. The review consolidates insights into ADA-SCID diagnosis and therapeutic strategies, proposing innovative approaches to enhance patient outcomes. Emerging treatments like gene editing and stem cell advancements hold significant promise, necessitating further research to address existing gaps and optimize care for ADA-SCID patients.