P-342: Early-onset diabetes mellitus as the inaugural manifestation of STAT1 gain-of-function mutation (IMD31C): a case report
A Coelho, T Ramos, L Cudizio, L E CalliariAbstract
Introduction
Immunodeficiency 31C (IMD31C), caused by heterozygous STAT1 gain-of-function (GOF) mutations, classically presents with chronic mucocutaneous candidiasis (CMC), autoimmune disorders and recurrent infections. Diabetes mellitus has been reported as a late feature, typically after candidiasis onset. Early-onset diabetes as the inaugural IMD31C manifestation has not been previously described.
Objectives
To report an atypical IMD31C presentation in which neonatal-onset diabetes mellitus preceded candidiasis and preceded molecular diagnosis.
Methods
Retrospective case report of a male patient at a pediatric referral center. Genetic workup included monogenic diabetes panel, MS-MLPA for neonatal diabetes and whole-exome sequencing (WES), all performed in 2025.
Results
A 2-year-10-month-old boy developed polydipsia, polyuria, weight loss and chronic diarrhea at age 3 months, presenting with diabetic ketoacidosis. Neonatal diabetes was suspected; sulfonylurea trial failed and insulin (basal-bolus, later CSII) was maintained. Candidiasis appeared concomitantly. At 14 months, hypochromic microcytic anemia was treated with iron. At 2 years, recurrent candidiasis prompted immunological evaluation: hypogammaglobulinemia (low IgG, IgA, IgM) and altered CD19; two IVIG infusions were given. Monogenic panel and MS-MLPA were normal. WES identified heterozygous STAT1 c.1398C>A (p.Ser466Arg), confirming IMD31C.
Conclusions
This case expands the IMD31C phenotypic spectrum: early-onset diabetes preceded candidiasis as the inaugural manifestation, a presentation not previously described. STAT1 GOF mutations should be considered in infants with unexplained early-onset diabetes associated with chronic diarrhea or immune dysregulation, even before candidiasis appears.