P-228: Neonatal diabetes mellitus due to mutation in the KCNJ11 changing a child and his father’s life
T de Lima Vitor, C Moura Almeida, P Lemgruber Xavier Mattoso Pavie, G Padilha Fontanella, H Morro, C Sousa Cortes, M dos Santos Pavani, A L Brunello, V Magalhães Domingues, L Hilário Bottura, M T Alves Sarti, V Kiill Suazo de Sant’Ana, R Liberatore Del Roio JuniorAbstract
Introduction
BACKGROUND:Neonatal diabetes mellitus (NDM) is a rare monogenic diabetes presenting in the first six months of life, caused by mutations that impair beta-cell function and insulin secretion. KCNJ11 variants are the main cause of permanent NDM.
Objectives
To describe a case of NDM with a heterozygous KCNJ11 mutation, highlighting clinical presentation, genetic findings, therapeutic response, and its diagnostic and treatment implications.
Methods
A 2-year-9-month-old male presented in early life with hypoactivity and reduced intake, progressing to severe diabetic ketoacidosis requiring ICU admission and mechanical ventilation. Despite basal-bolus insulin and later pump therapy, he had marked glycemic variability and recurrent hypoglycemia. Genetic testing identified a heterozygous KCNJ11 mutation, confirming NDM. Glibenclamide was initiated, resulting in progressive improvement, complete insulin withdrawal, and sustained glycemic control with adequate weight gain. Family investigation revealed that the father had a history of diabetes since childhood and was on insulin therapy, with poor glycemic control. Following the child’s diagnosis, genetic testing was performed in the father, which identified the same KCNJ11 mutation. Based on this result, insulin therapy was discontinued and sulfonylurea was initiated, leading to favorable outcomes and a significant improvement in glycemic control.
Results
Infants with early persistent hyperglycemia should undergo genetic testing for monogenic diabetes. In this case, the child’s diagnosis was crucial for identifying the mutation in the father, allowing diagnostic and therapeutic reclassification. Both were treated with sulfonylureas and achieved good glycemic control.
Conclusions
The case emphasizes early genetic diagnosis in NDM, enabling targeted therapy, insulin discontinuation, reduced glycemic variability and appropriate weight gain.