1710-P: A Case with Monogenic Diabetes Caused by RFX6 Mutation in a 14-Year-Old-Girl

Introduction: It is worthwhile to find new causes of monogenic diabetes to understand glycemic regulation as well as the management of diabetes mellitus. In previous times, diabetes mellitus in children and adolescents was usually type 1 diabetes which was caused by autoimmune beta cell destruction, but due to the increased prevalence of obesity, the incidence of type 2 diabetes was explosively increased in children and adolescents. The underlying mechanism of childhood-onset type 2 diabetes mellitus may be different to the adult-onset type 2 diabetes. Therefore, it is useful to conduct genetic study in children with type 2 feature.

Case: A 14 year-old-girl was diagnosed as having type 2 diabetes mellitus. Initially, she was presented with glycosuria, polydipsia, and polyuria. Initial HbA1c was 11.7%. She had no specific past medical problems. Her mother was already diagnosed as diabetes mellitus and on medication. her weight was 66.3kg (95 pecentile) and height was 148.3cm (3 percentile). Acanthosis nigricans was detected in neck and axillary areas. Blood glucose was 345 mg/dL, insulin was 27.2 uIU/mL, and C-peptide was 8.7 ug/dL, implying the presence of insulin resistance. There was neither ketonuria nor acidosis. Blood lipid profile showed 200 mg/dL of cholesterol, 45 mg/dL of HDL cholesterol, and 144 mg/dL of triglyceride. Thyroid function was normal. She was managed with long-acting insulin and oral hypoglycemic agent (Metformin^TM) and her HbA1c level became 9.3% at one year after the diagnosis. To find the candidate gene, targeted exome sequencing was performed which included 29 genes associated with monogenic diabetes. Nonsense mutation of the gene RFX6 was found (Tyr887*). The RFX6 gene mutation is known to contribute to beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels.

Conclusion: It may be recommended to perform the genetic test in childhood-onset type 2 diabetes mellitus to find the candidate gene of type 2 diabetes mellitus.