MON-231 Early Onset Autoimmune Endocrinopathies associated with Novel STAT-3 gain of function mutation
Year: 2025
Type: article
Abstract: Disclosure: R. Al Mefleh: None. K. McNerney: None. Background: The signal transducer and activator of transcription 3 (STAT3) is a key regulator in early development, cellular proliferation, survival, and differentiation. STAT3 Gain-of-Function (GOF) mutations are increasingly recognized as contributors to autoimmunity, potentially through impaired regulatory T cell development and the expansion and activation of T helper type 17 (TH17) cells. Dysregulated TH17 activity has been implicated in several autoimmune diseases, including Type 1 Diabetes Mellitus (T1D) and primary hypothyroidism. This report presents the case of a 6-month-old patient with early-onset T1D with autoimmune hypothyroidism associated with a STAT3 GOF mutation, discusses the role of STAT3 GOF mutations in autoimmune pathogenesis, and highlights the unique clinical features observed in this patient. Case Presentation: We report the case of a 6-month-old male infant with a history of recurrent severe infections requiring mechanical ventilation, failure to thrive, and atopic dermatitis. A comprehensive clinical assessment was undertaken, including a review of newborn screening, laboratory evaluations, and whole exome sequencing, which identified a potential STAT3 Gain-of-Function (GOF) mutation. During the course of his illness, the patient presented with severe dehydration and respiratory distress and was diagnosed with hyperglycemic ketoacidosis. Further investigations revealed positive GAD65 and anti-insulin antibodies, confirming a diagnosis of Type 1 Diabetes Mellitus. Early screening revealed elevated TSH levels and positive anti-thyroid peroxidase antibodies, indicating concurrent autoimmune hypothyroidism. Conclusion: This case highlights the importance of considering STAT3 GOF mutations or other mutations in patients with early-onset autoimmune conditions like Type 1 Diabetes mellitus, especially when accompanied by atypical features such as eczema and recurrent infections. It also emphasizes the need to consider an autoimmune basis in early-onset diabetes and hypothyroidism, particularly when other clinical indicators suggest such a link. Further research is essential to better understand the full spectrum of immune dysregulation associated with STAT3 mutations in pediatric autoimmune diseases. Presentation: Monday, July 14, 2025
Source: Journal of the Endocrine Society
Authors: Renad Al Mefleh, Kyle McNerney
Institution: Washington University in St. Louis
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,255
OpenAlex ID: W7093300064
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