Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis

Abstract

Congenital absence of the pancreas is an extremely rare condition. We participated in the care of a patient with an unusual presentation of neonatal diabetes attributable to agenesis of the pancreas. Additional clinical features of the patient included cardiac septal defects, gall bladder agenesis and duodenal malrotation. Appropriate institution of insulin, exocrine pancreatic supplements and surgical repair of the cardiac and intestinal anomalies resulted in the infant's survival. Of the reported cases of congenital pancreas agenesis, two cases have been ascribed to mutations in the insulin promoter factor-1(Ipf-1) gene. Deletion of the Ipf-1-homolog pdx-1 in mice results in the failure of pancreas to develop. Analysis of both exons of the Ipf-1 coding sequence from the presented patient's genomic DNA, however, did not identify a mutation. These results suggest that a congenital or genetic perturbation occurred in this infant most likely before the appearance of dorsal pancreatic bud in the 3 mm long embryonic stage, around the embryonic day 25 in human development, before the onset of Ipf-1 expression.

Agenesis of the Dorsal Pancreas and Associated Diseases

“…Complete agenesis of the pancreas is a rare congenital disorder, with permanent diabetes mellitus and malabsorption; this severely retards intrauterine growth and is usually fatal [3,4]. Other congenital developmental anomalies of the pancreas include annular pancreas, pancreas divisum, ductal anomalies, ectopic pancreas, congenital pancreatic cysts, and partial agenesis of the ventral or dorsal pancreas.…”

Pancreas Development and Regeneration

“…The dorsal and ventral pancreatic buds later fuse to form a single organ (this occurs on embryonic day (e) 12.5 in the mouse). Pancreatic bud outgrowth can be observed as early as day 25 of gestation in humans (Ashraf et al, 2005), e9.5 in the mouse (Slack, 1995), and 24 hours postfertilization in zebrafish (Figure 31.2;Field et al, 2003). In mammals, frogs, and chickens, both pancreatic buds consist of primary multipotent progenitor cells (MPCs) that generate exocrine and endocrine cells.…”

Neonatal Diabetes: Applying Molecular Biology to Patient Care

“…Mutations in the insulin promoter factor-1 (IPF-1) gene have been described as one cause of pancreatic agenesis. IPF-1 is the human homologue to the murine pdx-1 protein, an important regulator in insulin gene transcription and pancreatic development [3,12,13]. This protein is expressed in the early pancreatic bud, and initial studies showed that homozygous mutations in IPF-1 in mice caused pancreatic agenesis [14].…”

“…Pancreatic agenesis accounts for a rare number of reported cases of permanent NDM [12]. Mutations in the insulin promoter factor-1 (IPF-1) gene have been described as one cause of pancreatic agenesis.…”