Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections

This case report describes a 54-year-old woman with multiple endocrine autoimmune pathologies and recurrent mucocutaneous Candida spp. infections that were inappropriately attributed to her glycemic control. Following an allergic reaction over four decades later, the patient was referred to clinical...

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Main Authors: Sydney Sparanese, Rae Brager, David Fahmy, Jenny Garkaby
Format: Article
Language:English
Published: Bioscientifica 2025-07-01
Series:Endocrinology, Diabetes & Metabolism Case Reports
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Online Access:https://edm.bioscientifica.com/view/journals/edm/2025/3/EDM-25-0054.xml
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author Sydney Sparanese
Rae Brager
David Fahmy
Jenny Garkaby
author_facet Sydney Sparanese
Rae Brager
David Fahmy
Jenny Garkaby
author_sort Sydney Sparanese
collection DOAJ
description This case report describes a 54-year-old woman with multiple endocrine autoimmune pathologies and recurrent mucocutaneous Candida spp. infections that were inappropriately attributed to her glycemic control. Following an allergic reaction over four decades later, the patient was referred to clinical immunology. The combination of persistent Candida infections, autoimmune endocrinopathies, and a positive family history prompted investigation for an inborn error of immunity (IEI). Genetic testing revealed a novel, missense mutation in STAT1. Functional analysis confirmed enhanced STAT1 protein phosphorylation, confirming a gain-of-function phenotype that explained her infectious and autoimmune manifestations. She was started on the JAK inhibitor, ruxolitinib, with clinical improvement. This case underscores the shared molecular mechanisms between IEIs and autoimmune endocrinopathies and highlights the importance of early recognition of IEI in patients with unusual or treatment-refractory infections alongside autoimmune disease. Endocrinologists and primary care providers may be the first to encounter such patients and should consider referral for immunologic and genetic evaluation. Early diagnosis can reduce long-term morbidity and open the door to targeted therapies that address the root cause of immune dysregulation.
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spelling doaj-art-ad6dcfb549e54c8e8e52714779d1da832025-08-20T03:36:12ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732025-07-012025310.1530/EDM-25-00541Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infectionsSydney Sparanese0Rae Brager1David Fahmy2Jenny Garkaby3Department of Medicine, University of British Columbia, Vancouver, CanadaDepartment of Pediatrics, Division of Immunology, Allergy, and Dermatology, Hamilton Health Sciences, McMaster University, Hamilton, CanadaDepartment of Medicine, Clinical Immunology and Allergy, Hamilton Health Sciences, McMaster University, Hamilton, CanadaDepartment of Pediatrics, Division of Immunology, Allergy, and Dermatology, Hamilton Health Sciences, McMaster University, Hamilton, CanadaThis case report describes a 54-year-old woman with multiple endocrine autoimmune pathologies and recurrent mucocutaneous Candida spp. infections that were inappropriately attributed to her glycemic control. Following an allergic reaction over four decades later, the patient was referred to clinical immunology. The combination of persistent Candida infections, autoimmune endocrinopathies, and a positive family history prompted investigation for an inborn error of immunity (IEI). Genetic testing revealed a novel, missense mutation in STAT1. Functional analysis confirmed enhanced STAT1 protein phosphorylation, confirming a gain-of-function phenotype that explained her infectious and autoimmune manifestations. She was started on the JAK inhibitor, ruxolitinib, with clinical improvement. This case underscores the shared molecular mechanisms between IEIs and autoimmune endocrinopathies and highlights the importance of early recognition of IEI in patients with unusual or treatment-refractory infections alongside autoimmune disease. Endocrinologists and primary care providers may be the first to encounter such patients and should consider referral for immunologic and genetic evaluation. Early diagnosis can reduce long-term morbidity and open the door to targeted therapies that address the root cause of immune dysregulation.https://edm.bioscientifica.com/view/journals/edm/2025/3/EDM-25-0054.xmlautoimmunetype 1 diabeteshypothyroidismimmunodeficiencycase report
spellingShingle Sydney Sparanese
Rae Brager
David Fahmy
Jenny Garkaby
Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
Endocrinology, Diabetes & Metabolism Case Reports
autoimmune
type 1 diabetes
hypothyroidism
immunodeficiency
case report
title Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
title_full Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
title_fullStr Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
title_full_unstemmed Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
title_short Delayed diagnosis of STAT1 gain-of-function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
title_sort delayed diagnosis of stat1 gain of function variant in a patient with multiple endocrine autoimmunity and recurrent fungal infections
topic autoimmune
type 1 diabetes
hypothyroidism
immunodeficiency
case report
url https://edm.bioscientifica.com/view/journals/edm/2025/3/EDM-25-0054.xml
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AT davidfahmy delayeddiagnosisofstat1gainoffunctionvariantinapatientwithmultipleendocrineautoimmunityandrecurrentfungalinfections
AT jennygarkaby delayeddiagnosisofstat1gainoffunctionvariantinapatientwithmultipleendocrineautoimmunityandrecurrentfungalinfections