Abstract
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.
Similar content being viewed by others
References
Bariş Z, Eminoğlu T, Dalgiç B, Tümer L, Hasanoğlu A (2010) Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): case report with a new mutation. Eur J Pediatr 169:1375–1378
Bedlack RS, Vu T, Hammans S et al (2004) MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 29:364–368
Cardaioli E, Da Pozzo P, Malfatti E et al (2010) A second MNGIE patient without typical mitochondrial skeletal muscle involvement. Neurol Sci 31:491–494
Carod-Artal FJ, Herrero MD, Lara MC et al (2007) Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation. Eur J Neurol 14:581–585
Feddersen B, De La Fontaine L, Sass JO et al (2009) Mitochondrial neurogastrointestinal encephalomyopathy mimicking anorexia nervosa. Am J Psychiatry 166:494–495
Halter J, Schüpbach WM, Casali C et al (2010) Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant 46:330–337
Hiraki N, Udaka T, Yamamoto H, Kadokawa Y, Ohkubo J, Suzuki H (2010) Mitochondrial neurogastrointestinal encephalomyopathy associated with progressive hearing loss. J Laryngol Otol 124:1007–1009
Holden W, Orchard T, Wordsworth P (2003) Enteropathic arthritis. Rheum Dis Clin North Am 29:513–530
Lara MC, Valentino ML, Torres-Torronteras J, Hirano M, Martì R (2007) Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): biochemical features and therapeutic approaches. Biosci Rep 27:151–163
Lichtman SN, Wang J, Sartor RB et al (1995) Reactivation of arthritis induced by small bowel bacterial overgrowth in rats: role of cytokines, bacteria, and bacterial polymers. Infect Immun 63:2295–2301
Martí R, Spinazzola A, Tadesse S, Nishino I, Nishigaki Y, Hirano M (2004) Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays. Clin Chem 50:120–124
Martín MA, Blázquez A, Martí R et al (2004) Lack of gastrointestinal symptoms in a 60-year-old patient with MNGIE. Neurology 63:1536–1537
Massa R, Tessa A, Margollicci M et al (2009) Late-onset MNGIE without peripheral neuropathy due to incomplete loss of thymidine phosphorylase activity. Neuromuscul Disord 19:837–840
Mishkin D, Boston FM, Blank D, Yalovsky M, Mishkin S (2002) The glucose breath est: a diagnostic test for small bowel stricture(s) in Crohn's disease. Dig Dis Sci 47:489–494
Nishigaki Y, Martí R, Copeland WC, Hirano M (2003) Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. J Clin Invest 111:1913–1921
Nishino I, Spinazzola A, Hirano M (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283:689–692
Nishino I, Spinazzola A, Papadimitriou A et al (2000) Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol 47:792–800
Oztas E, Ozin Y, Onder F, Koral Onal I, Oguz D, Kocaefe C (2010) Chronic intestinal pseudo-obstruction and neurological manifestations in early adulthood: considering MNGIE syndrome in differential diagnosis. J Gastrointestin Liver Dis 19:195–197
Said G, Lacroix C, Planté-Bordeneuve V et al (2005) Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation. J Neurol 252:655–662
Scarpelli M, Cotelli MS, Mancuso M et al (2010) Current options in the treatment of mitochondrial diseases. Recent Pat CNS Drug Discov 5:203–209
Shoffner JM (2010) Mitochondrial neurogastrointestinal encephalopathy disease. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews. http://www.ncbi.nlm.nih.gov/books/NBK1179/
Yavuz H, Ozel A, Christensen M et al (2007) Treatment of mitochondrial neurogastrointestinal encephalomyopathy with dialysis. Arch Neurol 64:435–438
Acknowledgments
We kindly thank Dr. Michio Hirano from the Department of Neurology, Columbia University Medical Center, New York, NY, for thymidine phosphorylase biochemical assay and Dr. Alice Donati from the Unit of Hereditary Metabolic and Neuromuscular Diseases, Meyer Children Hospital, Florence, Italy, for thymidine and deoxyuridine assay in urine.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by: Shamima Rahman
Competing interest: None declared
Rights and permissions
About this article
Cite this article
Filosto, M., Scarpelli, M., Tonin, P. et al. Pitfalls in diagnosing mitochondrial neurogastrointestinal encephalomyopathy. J Inherit Metab Dis 34, 1199–1203 (2011). https://doi.org/10.1007/s10545-011-9332-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-011-9332-6