A Rare PTF1A Enhancer Mutation Causing Neonatal Diabetes Mellitus with Pancreatic Agenesis: Case Report and Considerations for Genetic Evaluation.

Introduction: Neonatal diabetes mellitus (NDM) is a rare disorder characterized by impaired blood glucose regulation that manifests before six months of age. Unlike autoimmune diabetes, NDM is caused by genetic mutations. One of the rarest causes of NDM is pancreatic agenesis, which results from mutations affecting the pancreas transcription factor 1A (PTF1A) gene and its enhancer. The following case report presents a rare instance of this condition.

Case presentation: This report describes a 2-year-old male child born to consanguineous Iranian parents, diagnosed with NDM due to pancreatic agenesis caused by a rare mutation in the PTF1A enhancer. Hyperglycemia was detected from the first day of life, and ultrasonography confirmed the absence of pancreatic tissue. Molecular analysis revealed homozygosity for the g.23508437A > G variant within the enhancer region of the PTF1A gene. At two years of age, with pancreatic enzyme replacement and insulin therapy, the patient exhibits normal neurological development, and his physical growth is at the 38th percentile.

Conclusions: Based on previous studies, the g.23508437A > G variant in the PTF1A gene enhancer region should be considered in cases of pancreatic agenesis. While whole-exome sequencing (WES) remains the gold standard for genetic diagnosis, it may fail to detect certain mutations. Therefore, targeted evaluation of PTF1A is essential when a genetic etiology is suspected.