A Case of Heterozygous INS Gene Missense Variant in Neonatal Diabetes with Beta-Cell Autoantibodies: Experience in...

Genetic analysis is essential for diagnosing, treating, and predicting complications in neonatal diabetes mellitus (NDM) but is unavailable in some regions. Sulfonylureas are effective for NDM caused by KCNJ11 or ABCC8 mutations, which are among the most common genetic causes; therefore, they are often given before genetic testing. Unfortunately, in certain ethnicities, this mutation rarely occurs. This report presents a case of NDM with a heterozygous INS gene missense mutation and positive pancreatic autoantibodies in a single individual.

A three-month-old boy, born to non-consanguineous parents, presented with diabetic ketoacidosis and bronchopneumonia. Initial management included intravenous insulin and antibiotics, followed by sulfonylurea and detemir insulin. The patient demonstrated a good response at 5 months of age, but by 11 months, glucose control deteriorated with increased HbA1c, positive pancreatic autoantibodies, and declining C-peptide levels over 10 months, necessitating a transition from sulfonylurea to basal - bolus insulin regimen. Genetic testing at age 4 years identified a heterozygous missense mutation in the INS gene (c.325T>C, p.Cys109Arg), confirming a diagnosis of permanent NDM.

In settings where genetic testing is limited, cautious sulfonylurea use based on clinical algorithms is recommended. Regular monitoring of sulfonylurea response, pancreatic autoantibodies, and β-cell function is essential to guide therapy adjustments.