SAT-607 New Diagnosis of Type 1 Diabetes in Wiskott-Aldrich Syndrome

Abstract Disclosure: C.K. Park: None. S. Zia: None. M.N. Rayan: None. L. Ghalib: None. Background: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder that typically presents with microthrombocytopenia, eczema, and recurrent viral or bacterial infections (1). Up to 40-70% of patients with WAS may develop concurrent autoimmune conditions. The defective regulatory T cells, hyperresponsive B cells, and chronic inflammatory state can put patients with WAS at higher risk for development of autoimmune disease. While vasculitides, autoimmune hemolytic anemia, and IgA nephropathy are recognized autoimmune features in WAS, type 1 diabetes is a more atypical manifestation (2). Clinical Case: A 37-year-old male reported recurrent infections and leukopenia since childhood. Bone marrow biopsy showed hypocellular marrow, and germline testing revealed gain-of-function mutation of the WAS gene. He was ultimately diagnosed with Wiskott-Aldrich syndrome. Given risk of malignant transformation, he was offered a bone marrow transplant. Work up for his transplant revealed significantly elevated blood glucose to >600 mg/dL and an A1c of 12.8%. He exhibited clinical symptoms of fatigue, polyuria, polydipsia, and a 20-pound weight loss. Antibody testing confirmed type 1 diabetes with elevated ZnT8 and GAD65 antibodies. C-peptide was 2.11. He was discharged on insulin and was able to initiate peripheral blood stem cell transplant for treatment of his WAS. Conclusion: To our knowledge, there are no prior case reports of ZnT8- and GAD65-positive type 1 diabetes in a patient with Wiskott-Aldrich syndrome. This case highlights the interplay between autoimmunity and immunodeficiency and underscores the need for multidisciplinary care in patients with rare immunodeficiency disorders. References: 1.Schurman SH, Candotti F. Autoimmunity in Wiskott-Aldrich syndrome. Curr Opin Rheumatol. 2003 Jul;15(4):446-53. doi: 10.1097/00002281-200307000-00012. PMID: 12819473.2.Cleland SY, Siegel RM. Wiskott-Aldrich Syndrome at the nexus of autoimmune and primary immunodeficiency diseases. FEBS Lett. 2011 Dec 1;585(23):3710-4. doi: 10.1016/j.febslet.2011.10.031. Epub 2011 Oct 25. PMID: 22036785; PMCID: PMC3580218. Presentation: Saturday, July 12, 2025