Feed

Autoimmune polyglandular syndrome type-1 (APS-1) results from mutations in autoimmune regulator (AIRE), a transcription factor that drives thymic expression of tissue-restricted antigens, thus enabling deletion of self-reactive thymocytes to maintain tolerance. APS-1 typically manifests with hypoparathyroidism, adrenal insufficiency, and candidiasis, but presentation varies. In this study, we characterized the clinical, genetic, and immunologic features of 18 new APS-1 patients and reviewed all reported cases to identify additional manifestations and mutational hotspots useful for targeted sequencing. We report three previously unpublished mutations, reduced T cell function, and diminished Treg numbers in our patients. Furthermore, we identified alopecia, thyroid disease, and diabetes mellitus as additional diagnostic clues, and revealed five recurrent variants that account for over 80% of known mutations. Our findings highlight additional clinical and laboratory features and emphasize key mutational hotspots that can accelerate the diagnosis to improve the timely and cost-effective identification of APS-1, especially in settings with limited awareness or resources.