Endocrine Abstracts

Mitochondrial diseases are rare conditions with a wide phenotypic range. The inability of dysfunctional mitochondria to produce sufficient ATP results in multi-organic defects dependent on high aerobic such as pancreas. The most common endocrine disease related to mitochondrial diseases is diabetes mellitus and it is thought to be secondary to insulin deficiency. A 26-year-old pregnant patient with 26 weeks gestational age was referred to an Endocrinology appointment due to diagnosis of diabetes de novo in pregnancy (oral glucose tolerance test - OGTT: fasting plasma glucose 187 mg/dl; 2-hour plasma glucose 417 mg/dl). The patient had no relevant past medical history or diabetes history in family and her regular medication were pregnancy vitamins. She denied catabolic symptoms. The actual HbA1C was 7.3% and pancreatic autoantibodies were negative. Before pregnancy, body index mass was normal. She was started on basal-bolus insulin therapy (insulin detemir 8 units plus insulin aspart 2+2+2). During medical follow-up, insulin aspart was suspended due to overall good postprandial glucose levels and basal insulin was maintained. Two weeks later the patient had a preterm delivery (36 weeks and 6 days); birth weight was 2.25 kilograms (4.94 lb). By this time, she discontinued insulin therapy and was started on metformin 700 mg b.i.d. and a genetic panel was conducted. It was identified a m.1644G>A variant in Mitochondrially Encoded tRNA Valine gene (MT-TV) with 82% heteroplasmy. This gene encodes transfer RNA that attaches specifically to valine (tRNA^Val) and therefore assists in protein synthesis involved in oxidative phosphorylation. ClinVar and Mitomap databases consider this variant as probably pathogenic and it has been associated to Leighs’ syndrome, hypertrophic cardiomyopathy and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Nevertheless, it has never been reported as a diabetes causative gene. Since this variant may reduce the amount of tRNA^Val available and impair mitochondrial function, the authors speculate if this mutation may be associated with diabetes surge.