Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare, fatal autosomal recessive disorder associated with variants in the TYMP gene, leading to nucleotide imbalance and subsequent mitochondrial DNA damage. Patients have a mean life expectancy of 35 years. MNGIE generally presents with gastrointestinal and neurological symptoms including cachexia, gastrointestinal dysmotility, ophthalmoplegia, neuropathy, myopathy, and leukoencephalopathy. Due to its diffuse and progressive nature, delayed and missed diagnosis is common.

A 25-year-old male with an extensive medical history including avoidant restrictive food intake disorder, GERD, recurrent diarrhea, type 2 diabetes mellitus, non-alcoholic steatohepatitis, scoliosis, mitral valve prolapse, pectus carinatum, and six years of left exotropia presented with one year of progressive diplopia. Further history revealed lifelong weakness and normal milestone attainment. Examination demonstrated muscular atrophy, bilateral ophthalmoplegia, reduced sensation to vibration in the toes, and facial, neck, and lower extremity weakness. Electromyogram and nerve conduction studies of the extremities showed mixed demyelinating-axonal polyneuropathy superimposed on proximal myopathy. Brain MRI revealed bilateral leukodystrophy. Neuromuscular gene panel demonstrated a novel, likely pathogenic variant (c.214+1G>T) and a variant of unclear significance (c.977G>A) in TYMP. Adjustment to the patient’s care included increased gastrointestinal screening for diverticula and dysbiosis, as well as MNGIE-targeted nutritional supplementation.