7916 Melas Syndrome: A Case Report

Abstract Disclosure: M. Yacobi Bach: None. M. Serebro: None. Y. Greenman: None. A 43-year-old married woman with two children of Ashkenazi descent was referred for endocrine evaluation due to suspected excess cortisol secretion. Extensive laboratory investigations yielded no evidence of pathological findings over time, raising the possibility of pseudo-Cushing syndrome related to a depressive episode, in contrast to a much less probable cyclic Cushing syndrome. As part of the endocrine follow-up, a comprehensive medical history was obtained, revealing a diagnosis of diabetes around the age of 30. Initially managed as type 2 diabetes, subsequent evaluation at our clinic raised the possibility of a mitochondrial disorder due to the combination of diabetes, early-onset sensorineural hearing loss, and premature ovarian insufficiency. The fact that patient's mother, has also been diagnosed with diabetes, hearing impairment and stroke-like episodes, further strengthened this hypothesis. Given the family history and the patient's clinical presentation, genetic testing was recommended, revealing a mitochondrial DNA mutation M.3243 A>G associated with MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) with a heteroplasmy level of 1 9%.Based on the genetic findings, a metabolic workup was initiated, leading to the recommendation of supplementing with ubiquinol, citrulline, arginine, taurine, riboflavin, and alpha-lipoic acid. Medications capable of inducing lactic acidosis, such as metformin and statins, were discontinued. SGLT2 inhibitors were also stopped due to concerns about ketoacidosis. The patient received guidance on emergency arginine therapy in suspected stroke-like episodes, characterized by altered consciousness, focal deficits, or seizures. Furthermore, comprehensive education on metabolic crises triggered by infections, psychological stress, or prolonged fasting was provided, emphasizing the importance of seeking medical attention for any changes in her baseline or cognitive status. The significance of updating healthcare providers on her medical condition before any surgical intervention was stressed. Genetic counseling was recommended for first-degree relatives. This case underscores the intricate interplay between mitochondrial disorders and endocrine manifestations, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and management. Presentation: 6/2/2024