Advances in Genetic and Molecular Understanding of Omenn Syndrome: Implications for the Future

The document from 2018 provides a comprehensive overview of Omenn syndrome, a severe combined immunodeficiency characterized by autoimmunity and a lack of B and T cells. It identifies hypomorphic mutations in RAG1 or RAG2 genes as the primary cause and discusses the clinical heterogeneity of the syndrome, influenced by genetic and environmental factors. The document highlights the importance of newborn screening for early diagnosis and improved transplant outcomes, as well as the potential of gene therapy, with ongoing clinical trials for genetic correction of autologous stem cells. It also suggests that targeting natural killer cells could reduce graft rejection. The document underscores the necessity of understanding the genetic and molecular mechanisms of Omenn syndrome to enhance patient treatment and outcomes, treating it as a pediatric emergency, and the role of environmental factors and other genetic defects in its pathogenesis. Management strategies include infection treatment, immunoglobulin replacement, skin care, and hematopoietic stem cell transplantation as the only curative treatment. The document concludes that advancements in newborn screening and gene therapy protocols are expected to further improve outcomes for patients with Omenn syndrome.