SUN-128 Novel Mutation in the HNF1A Gene in Siblings Previously Diagnosed with Type 1 Diabetes

Abstract

Abstract Introduction: Maturity Onset Diabetes of the Young (MODY) is a monogenic type of diabetes, frequently misdiagnosed as Type 1 diabetes. Previous studies have shown that MODY makes up about 1.1% of all diabetes cases among children 0-14 years. MODY can potentially be managed with dietary changes and/or oral medications. Case Presentation: A 16 year old girl who presented with elevated hemoglobin A1c was diagnosed with Type 1 diabetes with negative antibodies and started on insulin therapy. She also had negative screening for thyroid autoimmunity and celiac markers. Family history was positive for an older sister with antibody negative Type 1 diabetes, and their mother with diabetes of unknown etiology. The older sister was on insulin for 8 years. Given strong family history of diabetes and negative pancreas autoimmunity, the diagnosis of MODY was considered. Genetic testing on both sisters revealed a heterozygous variant in the HNF1A gene designated c.981del, suggesting MODY-3. This variant is predicted to result in a frameshift and premature protein termination (p.Ser328Valfs*14). To the best of our knowledge this mutation has not been reported as an etiology of MODY-3 and is expected to be pathogenic. Both siblings were started on oral sulfonylurea (SU) that has improved their hemoglobin A1c. The younger sister (index case) was completely weaned off insulin while the older sister had improvement in her diabetes control. Conclusion: We report a novel mutation in HNF1A gene in 2 siblings who were misdiagnosed as Type 1 diabetes and had significant improvement in their diabetes control after initiation of oral SU treatment. Strong family history of diabetes and negative autoimmune markers in affected individuals should alert the provider to consider MODY in the differential diagnosis particularly if the phenotype does not fit either type 1 or type 2 diabetes. Appropriately classifying type of diabetes will help choose the best treatment plan for the patient which can lead to improvement in quality of life and better health outcomes.