PEO1 Gene (Twinkle) Mutation and Multi-Organ Failure Following Propofol Infusion (IN7-1.005)

Abstract

Objective: Present a case of mitochondrial myopathy and multi-organ failure following propofol infusion. Background Mitochondrial DNA deletions are associated with a variety of clinical syndromes including chronic progressive external ophthalmoplegia (CPEO) due to nuclear as opposed to mitochondrial mutations. The nuclear PEO1 gene encodes for Twinkle, a helicase required for mitochondrial DNA replication and stability. Clinically, autosomal dominant Twinkle mutations are associated with CPEO. POLG mutations result in defects in the DNA polymerase gamma and can be associated with either autosomal dominant or autosomal recessive CPEO. Mitochondrial myopathies are associated with a sensitivity to propofol, and patients are more susceptible to developing a propofol infusion syndrome with resultant multi-organ dysfunction. Design/Methods: Literature review and illustrative case. Results: A 62-year old woman with a history of congenital ptosis and ophthalmoplegia was admitted for elective right eye enucleation for a corneal ulcer following levator resection. During the procedure, she was given propofol for anesthesia and the surgery was uneventful. Postoperatively, she developed a series of medical complications including Takotsubo cardiomyopathy, congestive heart failure, acute renal failure, and encephalopathy. She also developed dysarthria, bifacial and proximal muscle weakness, and difficulty weaning from the ventilator. Muscle biopsy was done showing a mitochondrial myopathy with scattered ragged red fibers and cytochrome oxidase negative muscle fibers. Genetic analysis showed nuclear mutations in the PEO1 and POLG genes. Conclusions: This patient had a mitochondrial myopathy presenting with CPEO, and after elective surgery, developed muti-organ dysfunction. She had the PEO1 mutation in addition to a POLG mutation. The literature on propofol use in mitochondrial myopathies is limited, but it has been associated with propofol infusion syndrome, and may have led to her poor clinical course. Disclosure: Dr. Harrison has nothing to disclose. Dr. Valerio has nothing to disclose. Dr. Buffam has nothing to disclose. Dr. Mezei has received personal compensation for activities with Genzyme as a speaker.