Congenital Immunodeficiencies in Infants: Mechanisms, Diagnosis, and Emerging Therapies

Congenital immunodeficiencies, also known as primary immunodeficiency disorders (PIDs), are a heterogeneous group of genetic disorders that impair immune function, resulting in increased susceptibility to infections, autoimmune diseases, and malignancies. These conditions arise from mutations affecting immune cell development, differentiation, or signaling pathways, leading to deficiencies in innate and adaptive immunity. This review explores the genetic and molecular mechanisms underlying congenital immunodeficiencies, emphasizing key mutations and their impact on immune system functionality. We discuss current diagnostic strategies, including newborn screening for severe combined immunodeficiency (SCID), immunophenotyping, functional immune assays, and genetic testing, all of which are crucial for early identification and tailored management. Additionally, we examine emerging therapeutic options, such as hematopoietic stem cell transplantation (HSCT), gene therapy using viral vectors or CRISPR-Cas9, and immunomodulatory approaches, highlighting their efficacy, limitations, and ongoing research efforts. While significant advancements in molecular diagnostics and targeted treatments have improved prognosis and survival rates, challenges remain in accessibility, cost, and potential treatment toxicities. Continued research and expanded newborn screening programs will be essential in optimizing outcomes for infants affected by these life-threatening disorders. Keywords: Congenital immunodeficiency, genetic mutations, immune dysfunction, gene therapy, hematopoietic stem cell transplantation, immunomodulation.