P-428: Unmasking monogenic diabetes: a case series of eight pediatric patients presenting atypically — lessons from India on diagnostic pitfalls and the impact of early genetic testing
M Agrawal, D J Vaishnav, C OzaAbstract
Introduction
Monogenic diabetes-encompassing Neonatal Diabetes Mellitus (NDM) and Maturity-Onset Diabetes of the Young (MODY) — accounts for 1–5% of pediatric diabetes but is frequently misdiagnosed in the acute care setting. Misdiagnosis leads to missed opportunities for sulfonylurea treatment, and delayed cascade family screening, particularly when we consider Hb1C for diagnosis, which may be normal in Neonatal diabetes. In India, where genetic testing access remains limited, this diagnostic gap is especially critical. Recognition of sentinel atypical features is the first and most essential step toward accurate diagnosis
Objectives
To describe the clinical phenotype, genetic spectrum, and management outcomes of eight pediatric patients with atypically presenting monogenic diabetes at a tertiary center in India
Methods
Retrospective case series (2020–2024).All patients underwent HbA1c, C-peptide, diabetes autoantibodies (GAD65, IA-2) & next-generation sequencing (NGS) monogenic diabetes panel.
Results
Age range:10 days–7 months.Presentations:DKA (n=3) failure-to-thrive with diarrhea/vomiting (n=3), isolated hyperglycemia (n=2). Key finding: HbA1c was disproportionately low (5.2–6.7%) despite blood glucose 300–400 mg/dL in 6/8 patients. All 8 were autoantibody-negative. NGS identified: 6q24-TNDM (n=2), SLC2A2/Fanconi–Bickel (n=1), PDX1/MODY4 (n=1), KCNJ11/permanent NDM (n=1); 3 cases under further analysis. Genetic diagnosis altered management in 5/8(62.5%): 2 achieved insulin independence(TNDM remission), 1 transitioned to sulfonylurea (KCNJ11).
Conclusions
Among the very few Indian series systematically characterizing monogenic diabetes, this study shows DKA does not exclude monogenic etiology, & low HbA1c relative to hyperglycemia is a critical red flag that is likely to be missed in an acute care setting.Early genetic testing changed management in the majority, averting lifelong unnecessary insulin.Monogenic diabetes screening should be integrated into routine pediatric diabetes workup.