Endocrine Abstracts

JOINT70

Our patient was diagnosed with gestational diabetes at age 21. At 28 years of age, she was diagnosed with type 2 diabetes. She was diagnosed in Poland moving to England shortly. The patient unfortunately knew very little about her biological family. She reported her mother had diabetes diagnosed as type 2 diabetes, but diet controlled which was diagnosed during pregnancy. She believed her mother possibly had a rarer form of diabetes. Her current medications were Gliclazide, Basal insulin, Linagliptin Dapagliflozin and Metformin. Her BMI at diagnosis was 22. 7. Whilst in UK, she was found to require insulin and tested negative for anti-GAD, anti-Islet cell antibodies, and had measurable blood C-peptide levels 7 years from diagnosis of diabetes. Her age and low BMI prompted a genetic screening revealing a NEUROD 1 mutation. It is believed that the patient is part of a large family in Poland with the same gene mutation. She has a son and daughter who do not have diabetes, so genetic testing is available for her children should she wish to proceed. There is no exact penetrance figure for the NEUROD1, but it is believed to be lower than the HNF1A mutation. There is no certainty as to whether the children will go on to develop diabetes and testing will not provide predictive onset for the children’s diagnoses of diabetes. It was advised to only test if the children became symptomatic and the mother was happy with this with prior counselling if genetic testing was required. NEUROD1 gene is expressed in pancreatic and neuronal cells, being associated with MODY type 6. NEUROD1 gene mutations have been reported in 20 families worldwide to date. Two mutations in NEUROD1, are associated with the development of type 2 diabetes in the heterozygous state. The first is a missense mutation while the second is a truncated polypeptide lacking the carboxy-terminal trans-activation domain, a region that associates with the co-activators CBP and p300. The clinical profile of patients with the truncated NEUROD1 polypeptide is more severe than that of patients with the Arg 111 mutation. A deficient binding of NEUROD1 or binding of a transcriptionally inactive NEUROD1 polypeptide to target promoters in pancreatic islets could lead to the development of type 2 diabetes. We surmise that patients with a family history of diabetes, normal BMI, early onset of diabetes, and no autoimmunity should be at least initially screened for a known MODY mutation.