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Year : 2017  |  Volume : 20  |  Issue : 3  |  Page : 328

Mitochondrial neurogastrointestinal encephalomyopathy syndrome with an unusual pattern of inheritance

1 Department of Neurology, Harbor- UCLA Medical Centre, Torrance, CA, USA
2 Department of Neurology, Olive View UCLA Medical Centre, Sylmar, CA, USA
3 Department of Neurology, USC Keck School of Medicine, Los Angeles, CA, USA

Date of Web Publication10-Aug-2017

Correspondence Address:
Shri Mishra
16111 Plummer Street, North Hills, CA 91343
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_117_17

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How to cite this article:
Trikamji B, Mohammadkhanli H, Rafiei N, Mishra S. Mitochondrial neurogastrointestinal encephalomyopathy syndrome with an unusual pattern of inheritance. Ann Indian Acad Neurol 2017;20:328

How to cite this URL:
Trikamji B, Mohammadkhanli H, Rafiei N, Mishra S. Mitochondrial neurogastrointestinal encephalomyopathy syndrome with an unusual pattern of inheritance. Ann Indian Acad Neurol [serial online] 2017 [cited 2020 Aug 12];20:328. Available from:


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) disease is a rare autosomal recessive disorder characterized by gastrointestinal dysmotility, external ophthalmoplegia, mitochondrial myopathy, peripheral neuropathy, and leukoencephalopathy.[1] Mutations in the thymidine phosphorylase (TYMP) gene (previously known as ECGF1) are known to cause MNGIE syndrome. We report a Hispanic family with confirmed diagnosis of MNGIE syndrome. The affected members included three of the four male siblings and their mother, maternal uncle, and maternal aunt [Figure 1]. Our patient is a 19-year-old male who was referred to neuromuscular clinic to rule out Charcot–Marie–Tooth disease, after having recurrent 5th metatarsal fractures bilaterally and chronic diarrhea. His family history revealed early deaths in the maternal side of his family, including his mother, maternal aunt, maternal uncle, and his older brother while the grandmother was unaffected. His older brother with disease was evaluated for mitochondrial disorders when he presented with ophthalmoplegia, myopathy, peripheral neuropathy, leukoencephalopathy on brain magnetic resonance imaging, and functional short gut syndrome with chronic diarrhea at the age of 10 years. His complete mitochondrial genome analysis revealed only a heteroplasmic mutation which codes for the mitochondrial encoded ribosomal subunit RNR2. Hence, the diagnosis of MNGIE was inconclusive. Our patient on neurological examination had normal mental status with intact cranial nerves. He had mild distal bilateral lower extremity weakness with atrophy and loss of large fiber sensation in his feet. His initial electromyography/nerve conduction studies showed moderate sensory motor polyneuropathy with mixed axonal and demyelinating features. Based on family history and clinical presentation, we decided to perform genetic testing for MNGIE syndrome despite the unusual pattern of inheritance. TYMP mutation revealed one predicted pathogenic mutation (c.1128-1153:26 bp deletion, heterozygous frameshift) and one of unknown clinical significance (c.977G>A; p. Gly326Asp, heterozygous missense). Although the inheritance pattern of MNGIE syndrome is autosomal recessive, we observed an unusual pattern of maternal inheritance in this family which delayed the diagnosis before referral of the family to our center. We postulated that severe TYMP dysfunction may have resulted in de novo mitochondrial mutations in germinal cells of the mother. The oldest offspring was probably spared due to younger age of mother at the time of pregnancy. We conclude that in clinically appropriate settings, diagnosis of MNGIE syndrome should not be dismissed due to a maternal pattern of inheritance as currently available interventions may be critical in the management of these patients.
Figure 1: Pedigree

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   References Top

Hirano M, Silvestri G, Blake DM, Lombes A, Minetti C, Bonilla E, et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. Neurology 1994;44:721-7.  Back to cited text no. 1


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