Neonatal diabetes due to a truncating RFX6 mutation in an extremely low birth weight preterm infant with...

Mitchell-Riley syndrome (MRS) is a rare autosomal recessive disorder caused by pathogenic variants in the RFX6 gene and characterized by neonatal diabetes, pancreatic hypoplasia with exocrine insufficiency, intestinal atresia, and hepatobiliary abnormalities. Despite increasing recognition of the syndrome, the number of reported cases remains limited and clinical management remains challenging. We aimed to report a preterm infant with an extremely low birth weight and a truncating RFX6 mutation to highlight the severe metabolic instability that may occur in such patients.

We report a preterm male infant born at 31 weeks of gestation with a birth weight of 880 g who presented with duodenal atresia, severe hyperglycemia beginning on postnatal day 4, chronic diarrhea, pancreatic exocrine insufficiency, and cholestasis. Imaging revealed gallbladder aplasia and pancreatic hypoplasia. Genetic analysis identified a homozygous truncating variant in the RFX6 gene (c.1573C>T; p.Arg525Ter), confirming the diagnosis of MRS. Despite intensive supportive therapy, including insulin infusion, nutritional support, and management of pancreatic insufficiency, the patient developed persistent metabolic instability and progressive liver dysfunction and died on postnatal day 195.

This case highlights MRS in an extremely low birth weight preterm infant and underscores the severe metabolic instability associated with truncating RFX6 mutations. Early recognition and genetic diagnosis are essential for appropriate management and genetic counseling.