LATE ONSET IPEX SYNDROME IN AN ADOLESCENT MALE

Abstract

<h3>Introduction</h3> Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder that presents with autoimmunity typically at an early age. We report the case of a 15-year-old male with common variable immunodeficiency (CVID) and bronchiectasis who presents with type 1 diabetes mellitus (T1DM) at age of 13. His severe presentation is concerning for an underlying monogenic immunodeficiency. This case highlights the late presentation of suspected IPEX syndrome in an adolescent male. <h3>Case Description</h3> Our patient with CVID and bronchiectasis presented with diabetes ketoacidosis at 13 years of age. He had a history of frequent sinopulmonary infections and was on immunoglobulin replacement therapy since 10 years of age for panhypogammaglobulinemia and specific antibody deficiency. Both immunologist and endocrinologist were concerned when T1DM developed and was difficult to treat. Genetic evaluation yielded hemizygous variant of uncertain significance in FOXP3[c.1036A>G(p.lle346Val)] in the forkhead domain. This variant is not present in Gnomad and deleterious by SIFT which prompted us to evaluate for IPEX. Immunophenotyping revealed reduced fraction CD4+CD25hiCD127low regulatory T cells (Tregs) with decreased forkhead box protein 3 (FOXP3) expression. More in-depth evaluations of his immune deficiency and immune dysregulation are pending. <h3>Discussion</h3> This case describes a late onset presentation of IPEX syndrome with features such as bronchiectasis, CVID, and late onset T1DM without other autoimmune manifestations. FOXP3 is essential for normal thymic Treg development. Missense mutations in nearby position Arg.347His has been described with T1DM but milder disease. The diagnostic approach of IPEX can be hindered by atypical phenotype as autoimmunity may present late.