Recently, bi-allelic mutations in the transcription factor RFX6 were described 
as the cause of a rare condition characterized by neonatal diabetes with 
pancreatic and biliary hypoplasia and duodenal/jejunal atresia. A male infant 
developed severe hyperglycemia (446 mg/dL) within 24 h of birth. Acute abdominal 
concerns by day five necessitated exploratory surgery that revealed duodenal 
atresia, gallbladder agenesis, annular pancreas and intestinal malrotation. He 
also exhibited chronic diarrhea and feeding intolerance, cholestatic jaundice, 
and subsequent liver failure. He died of sepsis at four months old while 
awaiting liver transplantation. The phenotype of neonatal diabetes with 
intestinal atresia and biliary agenesis clearly pointed to RFX6 as the causative 
gene; indeed, whole exome sequencing revealed a novel homozygous RFX6 mutation 
c.779A>C; p.Lys260Thr (K260T). This missense mutation also changes the consensus 
5' splice donor site before intron 7 and is thus predicted to cause disruption 
in splicing. Both parents, who were not known to be related, were heterozygous 
carriers. Targeted genetic testing based on consideration of phenotypic features 
may reveal a cause among the many genes now associated with heterogeneous forms 
of monogenic neonatal diabetes. Our study demonstrates the feasibility of using 
modern sequencing technology to identify one such rare cause. Continued research 
is needed to determine the possible cost-effectiveness of this approach, 
especially when clear phenotypic clues are absent. Further study of patients 
with RFX6 mutations should clarify its role in pancreatic, intestinal and 
enteroendocrine cellular development and explain features such as the diarrhea 
exhibited in our case.