Endocrine Abstracts

Introduction: Maturity onset diabetes mellitus of the young (MODY) is a form of monogenic diabetes characterized by pancreatic B-cell dysfunction. The most common subtypes are caused by mutations in the genes encoding glucokinase (GCK) and hepatocyte nuclear factor (HNF1a, HNF4a), although unidentified genes are also involved. Regulatory factor X6 (RFX6) is a transcription factor gene which has an important biological role in B-cell formation and function. Biallelic mutations in RFX6 cause Mitchell–Riley syndrome, characterized by neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, and intestinal atresia. Heterozygous RFX6 mutations have been identified in MODY cases.

Case Report: A 19-year-old female, with no past medical history, was referred to the emergency department for diagnostic evaluation of hyperglycemia, which was found in a medical checkup. She had been experiencing symptoms of diabetes mellitus (polyuria, polydipsia and weight loss of 5 kg) over the previous 2 months. Family members, including her sister, mother, and maternal grandfather had a history of diabetes. Her height was 156 cm, and her weight 59 kg, with a body mass index of 26 kg/m². Admission laboratory test reports included elevated plasma glucose and HbA1c levels (324 mg/dl and 11.4% respectively); and a diabetes mellitus diagnosis was made. No diabetic ketoacidosis was present. The patient was started on insulin therapy with a total dose of 17 units per day. She was evaluated in the Department of Endocrinology 1 year after the onset of diabetes. She had discontinued insulin therapy and was not receiving further treatment. HbA1c had decreased to 6.5% and her C-peptide level was 1.32 ng/ml. There were no islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) antibodies, or insulinoma-associated (IA-2) autoantibodies found. Genomic sequencing was performed in a panel which included 50 genes associated with monogenic diabetes mellitus. The analysis identified a heterozygous RFX6 mutation (c.541C>T, p.Arg181Trp) in the proband, which carried no pathogenic variants in other tested genes.

Conclusion: We describe a case of MODY due to a heterozygous RFX6 mutation p.Arg181Trp. RFX6 mutations have been associated with non-syndromic MODY with low penetrance and post-pubertal onset. Our report supports the evidence of causal relationship, although further studies are needed to define the association and to determine the appropriate therapeutic approach for these patients.