Abstract Details

Title Novel TYMP Mutation-causing Mitochondrial Neurogastrointestinal Encephalopathy as a Unifying Diagnosis Following the Onset of Diplopia in a Patient Previously Misdiagnosed with Disordered Eating: A Case Report

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 11-013

Background

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.

Objective NA

Design/Methods NA

Results

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.

Conclusions Even in patients with high access and utilization of medical resources, rare genetic diseases, especially mitochondrial diseases, can often be missed or mistaken for psychological processes. Delay in diagnosis can limit time-sensitive interventions and restricts the patient’s personal and family planning. In this case, cachexia and complex multisystem disease were interpreted as secondary to a restrictive eating disorder, and further diagnosis was not initiated until neurological symptoms manifested. This case highlights the risks of anchoring bias, especially in patients with psychiatric diagnoses, as well as the role of the neurologist in considering unifying diagnoses for patients with multisystem disease.

Authors/Disclosures
Kevin C. Donohue PRESENTER	Mr. Donohue has nothing to disclose.
Min Kang, MD (University of California, San Francisco)	Dr. Kang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Kang has received research support from UCSF resource allocation program .