Restricted accessCase reportFirst published online 2025-7
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) Phenotype Associated With Unique Compound Heterozygous POLG Variants: Case Presentation and Review of the Literature
We report a teenage patient with a delayed diagnosis of compound heterozygous POLG pathogenic variants [(POLG c. 1943 C>G, p.P648R) and (POLG c. 679 C>T, p.R227W)] who presented with fatigue and neuropathy, as well as long standing malnutrition and cachexia, erroneously attributed to an eating disorder. She experienced multiple bowel perforations and pathologic examination revealed jejunal diverticula and features of visceral neuromyopathy. In addition to ganglion cell mega-mitochondrial inclusions, there were multiple foci of interrupted muscularis mucosae, an alteration not previously recognized in the intestines of patients with primary mitochondrial disorders. We provide a detailed account of the gastrointestinal pathologic findings in this patient and compare with prior cases of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) phenotypes.
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