ESPE Abstracts (2016) 86 RFC5.6

aHôpital Universitaire Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris, Paris, France; bUniversity Paris Diderot, Sorbonne Paris Cité, Paris, France; cDépartement de génétique, APHP, Hôpital Universitaire Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France; dService endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital universitaire Necker Enfants Malades Paris, Assistance Publique-Hôpitaux de Paris, Paris, France; eInserm U1016, Institut Cochin, Paris, France

Background: Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome associating neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis, duodenal atresia, and severe chronic diarrhea. Nine cases have been reported so far and the condition has a poor prognosis with five of nine patients died before the age of 6 months.

Objective and hypotheses: To report on the clinical management and outcome of two new cases from two independent families.

Results: The two patients were from first degree consanguineous families, had severe SGA and an antenatal diagnosis of duodenal atresia. Diabetes was diagnosed at day one and treated with intra-veinous insulin for several months, before switching to subcutaneous with doses between 0.6 and 0.8 UI/kg per d. In patient 1, abdominal imaging showed pancreatic tail and body agenesis, gallblader agenesis, and a normal biliary tract. He had moderate hepatic cytolysis without cholestasis. The chronic and severe diarrhea could only be controlled with total parenteral nutrition, with watery diarrhea recurring at every attempt to introduce enteral nutrition at the age of 30 months, needing a prolonged hospitalization. Patient 2 had hypoplastic pancreas, duodenal and jejunal atresia with gallblader agenesis and necrotizing enterocolitis after surgery. He had no cholestatic disease and was on parenteral nutrition until the age of 12 months due to the severe diarrhea. He has a normal enteral diet at 8 years. The diagnosis was confirmed in the two cases with homozygous mutations in the RFX6 gene: p.Arg181Trp in patient 1 (recently described in another family) and p.Val506Gly, never described previously in patient 2.

Conclusion: These patients demonstrate that an aggressive supportive management of patients with RFX6 mutations can result in improved outcome than previously described. The understanding of RFX6 role will open new therapeutic avenues, particularly the use of drugs that interfere with the gut endocrine system.

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