A Young Adult Male with Chronic Mucocutaneous Candidiasis (CMC) with Signal Transduction and Activator of Transcription 1 (STAT 1) Mutation and Progressive Multifocal Leukoencephalopathy (PML)

Abstract

M O N D A Y 600 Variable Presentations of Gain of Function STAT1 Mutations within a Single Institution with Features Beyond Chronic Mucocutaneous Candidiasis Sheila M. Bina, MD, Jenni Y. Yoon, MD, Jennifer W. Leiding, MD; University of South Florida, St. Petersburg, FL. RATIONALE: Gain of function (GOF)mutations in signal transducer and activator of transcription 1 (STAT1) are a major cause of chronic mucocutaneous candidiasis (CMC). Susceptibility to viral, bacterial, fungal, and mycobacterial infections can also occur. In addition to infection susceptibility, patients with GOF-STAT1 mutations suffer from many other manifestations. METHODS: Retrospective chart reviews were performed on 5 patients with GOF-STAT1 mutations to identify specific infectious susceptibility and other immunologic manifestations. RESULTS: All 5 patients identified have mutations in the coiled-coiled or DNA binding domains of STAT1, all consistent with gain of function. Four patients have CMC, 1 has recurrent herpes simplex virus stomatitis, 1 had Mycobacterium fortuitummediastinal lymphadenitits, and 2 have recurrent sinopulmonary infections. One patient presented at 5 months of age with immunodysregulation-polyendocrinopathy-enteropathy-X-linked (IPEX) like manifestations including severe refractory diarrhea, diabetes, and failure to thrive. Successful matched unrelated bone marrow transplant was performed at 3 years of age. In addition to CMC, one patient had a giant hand granuloma caused by Trichopyton tonsurans. Other non-infectious manifestations include generalized seizures, autoimmune hemolytic anemia, recurrent thrombosis, and squamous cell carcinoma. CONCLUSIONS: In addition to CMC, these patients demonstrate broad infectious susceptibility and many other manifestations of GOF-STAT1 mutations including IPEX-like disease, vascular disease, autoimmunity, and malignancy.