Neonatal diabetes attributable to pancreatic agenesis is an extremely uncommon congenital disorder. We report a variant of pancreatic agenesis in a neonate complicated by other congenital birth defects. A full term white female infant was born manifesting intrauterine growth retardation, atrial- and ventricular-septal defects, and diabetes on day I of postnatal life. Initial investigation did not reveal evidence of islet autoimmunity. Insulin and C-peptide levels were undetectable. CT scan of the abdomen revealed congenital agenesis of the pancreas. The patient was initiated on insulin on postnatal day two. At 6 days of age the patient developed a pneumoperitoneum secondary to a small perforation at the proximal jejunum. Exploratory laparotomy revealed incomplete duodenal malrotation and absence of pancreas and gall bladder. Surgical repair of the intestinal perforation and cardiac defects was subsequently performed. Pancreatic enzyme supplementation was begun on day 12 of postnatal life and the patient has done well subsequently on an insulin infusion pump. There are only 3 reported cases of pancreatic agenesis in which genetic defects were examined with two cases revealing mutations in the pancreatic duodenal homeobox gene-1 (PDX-1), each in either of the two exons. PDX-1 is a transcription factor involved in regulating multiple genes in islet cells, including insulin gene expression. PDX-1 deficiency in mice is lethal early as a result of pancreas agenesis and neonatal diabetes. Heterozygous mutations in the PDX-1 gene in mice and humans result in glucose intolerance and diabetes. We examined the PDX-1 gene sequence in our case patient to determine if coding mutations were present in either of the two exons of the PDX-1 gene locus. Genomic DNA was isolated from peripheral blood of the patient. PCR primers flanking the regions of previously reported mutations were used to amplify PCR fragments of ⋍ 500 base pairs each and the fragments were subjected to dideoxy DNA sequencing. We did not identify any mutations in the PDX-1 gene locus. Our patient is unique from other reported cases in the phenotypic constellation of abnormalities and our investigation suggests that factors expressed upstream of PDX-1 expression may be required for proper endoderm development. Subsequent studies are required to elucidate causative candidate genes underlying in the etiology of pancreatic agenesis in our case patient.
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