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

## TL;DR

A rare mutation in the PTF1A enhancer causes neonatal diabetes with pancreatic agenesis, highlighting the need for targeted genetic testing.

## Contribution

Identifies a novel PTF1A enhancer mutation as a cause of neonatal diabetes with pancreatic agenesis.

## Key findings

- A homozygous g.23508437A > G variant in the PTF1A enhancer causes pancreatic agenesis and neonatal diabetes.
- The patient showed normal neurological development with enzyme replacement and insulin therapy.
- Whole-exome sequencing may miss enhancer mutations, necessitating targeted PTF1A evaluation.

## Abstract

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.

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.

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.