Pseudomyasthenia Gravis: An uncommon and potentially hazardous mimicker of mitochondrial disease (5427)

Objective: - Background: The spectrum of mitochondrial disease is broad. Definitive diagnosis is limited by low sensitivity diagnostic testing and the lack of evidence-based diagnostic guidelines. This may lead to diagnostic delay and exposure to unnecessary and hazardous treatment. Design/Methods: We describe a 38-year old man with unexplained diarrhea since age 22, distant paroxysmal attacks of left hemiparesis, brain imaging interpreted as lacunar infarction and a presumed diagnosis of antiphospholipid antibody syndrome. At age 24, there was onset of asymmetric ophthalmoparesis, ptosis, and dyspnea. Myasthenia gravis (MG) serology, repetitive nerve stimulation testing, and single fiber electromyography were unrevealing. A muscle biopsy and magnetic resonance spectroscopy for lactate were normal. The patient was ultimately treated for presumed seronegative myasthenia gravis with prednisone, intravenous immunoglobulin, plasmapheresis and transsternal thymectomy after a failed thoracoscopic approach. Fifteen years after onset, mtDNA analysis revealed a novel homoplasmic m.10192C>A variant (S45T) in the mitochondrial ND3 gene. There are numerous previously reported patients with demonstrated pathogenic variants affecting the highly conserved 45th codon. Patients with the m.10191 (S45P) variant are associated with a broad clinical spectrum of mitochondrial disease. The patient’s parents were deceased. Coenzyme Q10 muscle determination was low in the proband. We conclude the detected novel ND3 sequence variant is likely pathogenic. Immunosuppressive therapy was stopped in favor or a mitochondrial cocktail with subjective improvement. Results: This case expands knowledge about pathogenic mtDNA variants in the ND3 gene and the clinical spectrum of disease associated with missense mutations affecting codon 45. Conclusions: Mitochondrial disease can mimic MG. This may lead to unnecessary medical and surgical therapy. The increased availability and more accurate interpretation of genetic testing is likely to reduce diagnostic delay and unnecessary treatment in the future. A diagnosis of seronegative MG should be made with caution in patients with multiple system involvement. Disclosure: Dr. Mingbunjerdsuk has nothing to disclose. Dr. Pasnoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, Alexion Pharmaceuticals, Argenx Pharmaceuticals, and Momenta Pharmaceuticals. Dr. Statland has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Strongbridge, Acceleron, Regeneron, and Sanofi.Dr. Jawdat has nothing to disclose. Dr. Jabari has nothing to disclose. Dr. Barohn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NuFactor and Momenta Pharmaceutical. Dr. Barohn has received research support from PTC Therapeutics, Ra Pharma, Orphazyme, Sanofi Genzyme, FDA OOPD, NIH, and PCORI. Dr. Dimachkie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dimachkie recently served as a consultant or on the speaker’s bureau for Alnylam, ArgenX, Audentes, CSL-Behring, Sanofi Genzyme, Momenta, NuFactor, RMS Medical, Shire Takeda and Terumo.. Dr. Dimachkie has received research support from Dr. Dimachkie received grants from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, CSL-Behring, FDA/OPD, GlaxoSmithKline, Genentech, Grifols, MDA, NIH, Novartis, Genzyme, Octapharma, Orphazyme, UCB Biopharma, Viromed an.Dr. Farmakidis has nothing to disclose.