Endocrine Abstracts

Neonatal diabetes mellitus (NDM) is a rare monogenic disorder (incidence ~1:100,000). Mutations in KCNJ11 and ABCC8 genes are common causes. Timely genetic diagnosis is crucial to differentiate NDM from Type 1 diabetes, predict clinical course, and guide management, often enabling transition from insulin to oral sulfonylurea therapy. We present a male infant, admitted at three weeks of age with vomiting and incidental hyperglycaemia (16.6 mmol/l). A paternal diabetes history was noted. Initial management involved observation and home monitoring. Despite the high initial reading, subsequent glucose levels fluctuated (5.6-13.9 mmol/l), creating an ambiguous clinical picture. This case highlights a critical diagnostic challenge: NDM can present with fluctuating hyperglycaemia not immediately warranting aggressive intervention. It underscores the necessity of maintaining a high index of suspicion and pursuing genetic testing even with ambiguous presentations. Genetic testing serves as a definitive tool when clinical presentation is unclear, providing clarity for immediate management and long-term prognosis. The paternal diabetes history, initially coincidental, proved a crucial clue supporting genetic testing. Investigations showed negative Type 1 diabetes autoantibodies and an HbA1c of 41.5 mmol/mol. Genetic testing confirmed a heterozygous pathogenic missense variant in the ABCC8 gene, diagnostic of transient neonatal diabetes. This definitive diagnosis allowed a targeted management plan focused on monitoring. The family was counselled on the condition’s transient nature, high remission likelihood, and significant relapse risk in adolescence/adulthood. A clear protocol for initiating sulfonylurea therapy upon relapse was established. The infant is currently thriving under regular follow-up. This case demonstrates that NDM can present with subtle, fluctuating glycaemic patterns, posing a diagnostic pitfall. It champions early genetic testing as the definitive tool to reveal the underlying aetiology. This approach is paramount for accurate diagnosis, predicting disease trajectory, and implementing personalized, effective long-term management.

Key Learning Points:

• NDM may present with variable glucose levels that don’t consistently meet diabetic thresholds.

• Family history of diabetes should prompt consideration of monogenic diabetes.

• Early genetic testing is crucial for definitive diagnosis and management planning.

• Sulfonylurea therapy is the preferred treatment for K-ATP channel mutations.