Abstract
Background Neonatal diabetes along with congenital anomalies like duodenal atresia, tracheoesophageal fistula, intra uterine growth retardation, extrahepatic biliary obstruction and hypoplasia of pancreas is a very rare occurrence with evidence linking it to RFX6 gene mutation. Their presence in newborn babies necessitates a detailed genetic evaluation and multidisciplinary management. Here, we present a preterm baby with persistent neonatal hyperglycemia and gastrointestinal anomalies similar to cases associated with Mitchel Riley/Martinez Frias syndrome.
Case Report(s) In our case the baby had multiple congenital anomalies along with neonatal diabetes which were managed by a multidisciplinary team. Neonatal diabetes management proved to be challenging with frequent blood glucose monitoring and continuous insulin infusion.
Around half the cases of permanent neonatal diabetes mellitus shows a gene mutation which usually affects pancreas beta cell development and function.1 The most frequent gene with identified mutations is KCNJ11 and to a lesser extent GCK, ABCC8, and HNF1β.
Martinez Frias syndrome is a rare condition characterized by duodenal atresia, tracheoesophageal fistula, intra uterine growth retardation, extrahepatic biliary obstruction and hypoplasia of pancreas with neonatal diabetes. It is inherited in an autosomal recessive manner and has evidence linking it to RFX6 gene mutation.
RFX6 gene is involved in the development of the gut and pancreatic tissue. There are studies showing the involvement of this gene in the differentiation of islet cells and regulation of transcription factors involved in beta cell function thereby affecting insulin production.
Mitchell-Riley syndrome is considered to be an association of a particular phenotype of Martinez-Frias syndrome and it was suggested that both represent an RFX6 malformation complex.
There is a case reported by Concepcion JP et al where a baby with neonatal diabetes, gallbladder agenesis, duodenal atresia and intestinal malrotation was associated with RFX6 gene mutation.
Another recent case of neonatal diabetes, duodenal atresia and progressive neonatal cholestasis reported from the middle east showed a similar mutation.
A study by Mitchell et al described association between neonatal diabetes and intestinal atresia. No conclusive evidence of genetic mutations could be obtained in this study.
Conclusion(s) The presence of neonatal diabetes along with intestinal atresia and progressive cholestasis should raise the suspicion of Mitchell Riley/Martinez Frias syndrome. Owing to the increased morbidity and mortality in these children, prompt genetic evaluation especially the associated mutation in RFX6 gene and early detection is essential to establish a diagnosis and for appropriate counselling of the family.
There is a need for further studies exploring the linkage of gene mutations specifically that of RFX6 and its association with congenital anomalies involving the gastrointestinal system.
