Pitfalls in diagnosing mitochondrial neurogastrointestinal encephalomyopathy

J Inherit Metab Dis. 2011 Dec;34(6):1199-203. doi: 10.1007/s10545-011-9332-6. Epub 2011 Apr 19.


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic options (peritoneal dialysis, allogeneic stem cell transplantation, enzyme replacement) makes it necessary to diagnose the disease early, which is not always achieved due to the difficulty in recognizing this disorder, especially in case of atypical presentation. We describe three MNGIE patients with atypical onset of the disease. In the first patient the main symptoms were long-standing chronic fever, recurrent acute migrant arthritis, and gastrointestinal disorders mimicking autoimmune or inflammatory intestinal diseases; the second patient complained only of exercise intolerance and muscle cramps, and the third patient had a CIDP-like polyneuropathy. This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies.

Publication types

  • Case Reports

MeSH terms

  • Abdominal Pain / etiology
  • Adult
  • Diagnosis, Differential
  • Female
  • Humans
  • Intestinal Pseudo-Obstruction / complications
  • Intestinal Pseudo-Obstruction / diagnosis*
  • Intestinal Pseudo-Obstruction / etiology
  • Intestinal Pseudo-Obstruction / genetics
  • Male
  • Mitochondrial Encephalomyopathies / complications
  • Mitochondrial Encephalomyopathies / diagnosis*
  • Mitochondrial Encephalomyopathies / genetics
  • Muscular Dystrophy, Oculopharyngeal
  • Mutation / genetics
  • Ophthalmoplegia / congenital
  • Thymidine Phosphorylase / genetics


  • Thymidine Phosphorylase

Supplementary concepts

  • Visceral myopathy familial external ophthalmoplegia