MON-122 Familial Clinical Heterogeneity Manifested by the Presence of Either Diabetes or Deafness in a Pedigree of a Patient with Maternally Inherited Diabetes Mellitus and Deafness and Mitochondrial DNA M.3243a>G Mutation

Introduction: Mitochondrial DNA mutation is a rare cause for diabetes mellitus (DM) and deafness that is often misdiagnosed as type 1 or type 2 DM. Unique management issues, associated comorbidities and fertility plans require proper diagnosis. Proband: a 25 year-old female presented with a fasting glucose 205 mg/dl, Hb A1c 8.5% with intolerance to metformin. She has been previously diagnosed with sensorineural hearing loss. Her physical examination was unremarkable, except for a BMI of 20kg/m(2) and a short stature. Her parents were not blood-related. The family history was notable for several relatives with either diabetes or deafness. Her twin sister had prediabetes, her older sister had deafness, her brother had muscle cramps and her mother had both DM and hearing loss, and was also diagnosed with "fibromyalgia". From the mother side; her grandmother had DM, her aunt had deafness and her daughter had DM, 2 uncles had DM. GAD antibodies, Islet cell antibodies and Zinc transporter 8 antibodies were negative. Renal function was normal. She responded well to basal insulin treatment, with an achieved Hb A1c of 7%. Her genetic workup identified a mutation in the mitochondrial DNA m.3243A>G which is associated with MIDD (maternally inherited diabetes and deafness) and MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes). The following specific recommendations were made, which differ from the standard practice and guidelines in the care of classical type 1 or type 2 diabetes: 1) avoid metformin; 2) rigidly maintain adequate carbohydrate consumption when ill, as stroke- like episodes have been described in this condition during acute illness when carbohydrate supply was inadequate; 3) use Coenzyme Q10 which might enhance insulin secretion and potentially improve symptoms of myopathy. 4) attempt not to postpone fertility due to the risk of premature ovarian failure; 5) for pregnancy planning, consider "three parent IVF" with mitochondria and cytoplasm from a donated ovum, thus potentially avoiding transmitting the defect. Conclusion: Diagnosis of MIDD should be considered in subjects with family history of premature deafness and diabetes, not necessarily in the same subjects. The correct diagnosis may offer multiple therapeutic advantages. With accurate genetic diagnose, appropriate therapy, family screening, genetic counseling and surveillance for existing and future complications can be applied.