RECURRENT FUNGAL INFECTIONS FROM BIRTH TO ADULTHOOD: UNKNOWN DIAGNOSIS UNTIL GENETIC TESTING FOR STAT-1 VARIANTS

Abstract

<h3>Introduction</h3> Signal transducer and activator of transcription 1 (STAT-1) is a transcription factor that plays key roles in cell viability and pathogen responses. Mutations in STAT-1 result in differing degrees of susceptibility to viral, fungal and bacterial infections, vascular alterations, failure to thrive, and autoimmunity. We report a case of STAT-1 variant presenting with a life-long history of recurrent fungal infections where the diagnosis required genetic testing. <h3>Case Description</h3> A 33-year-old man presented for an evaluation of recurrent fungal infections. He experienced oral thrush, tinea pedis, tinea corporis, and onychomycosis since infancy. He was hospitalized twice for Candida esophagitis requiring IV antifungals. He required treatments with oral antifungals every few months, as he was refractory to topical treatments. He had no bacterial or viral infections, and otherwise unremarkable past medical history. He had thorough workups through multiple specialists with no diagnosis made as his immunologic laboratory studies were normal. However, his 4-year-old son was diagnosed with chronic mucocutaneous candidiasis (CMCC) and had genetic testing showing a STAT-1 variant (c.1159A>G (p.Thr387Ala)). The patient then underwent genetic testing which revealed the same pathogenic STAT-1 variant. Further evaluation showed normal T-cell mitogen studies, total IgG/A/M/E, IgG subclass levels, and vaccine responses. Flow cytometry showed mild B-cell lymphopenia and normal T/NK cells. <h3>Discussion</h3> Patients with pathogenic STAT-1 variants can present with variable infection histories and normal immunologic testing. This case highlights the importance of genetic testing for patients presenting with CMCC regardless of normal immunologic testing to identify a specific diagnosis and defects associated with CMCC.