Necrotizing enterocolitis in an infant with Omenn syndrome

Omenn syndrome (OS) is a rare disorder within the combined immunodeficiency family that is characterized by a diffuse exudative, erythematous rash, lymphadenopathy, hepatosplenomegaly, alopecia, and failure to thrive. Specific lab findings unique to OS include hypereosinophilia, elevated IgE, excess production of oligoclonal T-cells and near-to-absent B-cells. Much remains elucidated about the underlying genetic cause of OS. Until recently, it was felt that the disease was primarily caused by mutations of the RAG1 or RAG2 genes. The type of mutation of the RAG1 and RAG2 genes in patients with OS affects the degree of functioning variable (diversity) joining [V(D)J] recombination activity, which is critical to the development of lymphoid cell receptor diversity. New work has also shown that thymic tissue in OS patients demonstrates a severe defect in the expression of the autoimmune regulator element. This may contribute to the development of autoreactive T-cells that are felt to be the causative agent of a number of the clinical hallmarks unique to OS. The genetic spectrum of OS was further expanded when a patient with clinical and immunologic features consistent with OS, without RAG mutation, was found to have mutations in both alleles coding for ARTEMIS, a key V(D)J recombination/DNA repair factor. Regardless of the underlying cause, early recognition is critical because patients die at a very young age without bone marrow transplantation. We describe an infant diagnosed with OS post-mortem in which death was directly related to the development of necrotizing enterocolitis.