ESPE Abstracts

Background: Pancreatic agenesis has been reported as a cause of neonatal diabetes. Most commonly it was associated with severe neurodevelopmental problems caused by homozygous mutations in the transcription factor PTF1A. Isolated pancreatic agenesis was related to biallelic mutations in an enhancer located near PTF1A gene, which suggests that the enhancer is tissue specific to the pancreas. PDX1 is another transcription factor gene in which biallelic mutation resulted in neonatal diabetes in the absence of exocrine pancreatic insufficiency.

Case report: 2 siblings (Currently, 16 and 13 years old) from consanguineous parent diagnosed with early onset neonatal diabetes. They presented on the first 2 days of life with high blood glucose not related to stress or medications and started on Insulin during the first week. Insulin doses were adjusted based on their need. Clinically, there were no dysmorphic features or impaired neurological manifestations. Throughout their clinical course, they were evaluated for short stature and failure to thrive. Celiac screening was positive in the older boy but negative for the girl. They were complaining of recurrent foul-smelling diarrhea, diagnosed with malabsorption and ADEK vitamins deficiency and started on replacement therapy. US abdomen showed pancreatic agenesis. With treatment, their diabetes was controlled, but they ended-up short and the diarrhea persist. Whole exome sequencing showed a homozygous missense mutation (exon1: c.571C>A: p.P191T) in both siblings causing isolated pancreatic agenesis. This mutation had been reported once as hypomorphic PTF1A mutation in four individuals from two separate families from Saudi Arabia and Kuwait with same presentation.

Conclusion: Hypomorphic PTF1A missense mutations can cause isolated pancreatic agenesis. This mutation should be considered in patients presenting with neonatal diabetes without neurological manifestations especially in a child with consanguineous parent. Patients with this mutation has been reported in our region which could be a founder mutation.