Susceptibility to MELAS Exacerbations in a POLG1 Mutation Carrier (P5.264)

We describe a case of a 46-year-old woman who presented with expressive aphasia, disorientation, and inappropriate laughter. She notably had a history of bilateral sensorineural hearing loss and two stroke-like episodes in her 30s characterized by left hemiparesis. Over the preceding six months, she experienced rapidly progressive vision loss, headaches, and an episode of non-convulsive status epilepticus. Incidentally, she had undergone renal transplantation nine months earlier for autosomal dominant polycystic kidney disease, and was on immunosuppressive therapy with two calcineurin inhibitors—cyclosporine and tacrolimus—in succession. These were held on admission given suspicion for PRES. Serial MRIs revealed cortical temporo-parieto-occipital T2/FLAIR hyperintense lesions with corresponding diffusion restriction that remitted and reappeared in new non-vascular distributions. Serum and CSF lactate and pyruvate were elevated, and a muscle biopsy indicated ragged red fibers, all of which supported a clinical diagnosis of MELAS. Exome sequencing ultimately revealed a novel heterozygous mutation in POLG1. Treatment with antipsychotics, initiated before establishing the diagnosis, resulted in no clinical improvement. Over the course of one month, off of calcineurin inhibitors and with the initiation of levocarnitine, the patient’s mental status and MRI lesions improved. DISCUSSION Calcineurin inhibitors have been demonstrated to impair mitochondrial respirat...
Source: Neurology - Category: Neurology Authors: Tags: General Neurology: Genetics Source Type: research