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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00669

Mitochondrial Neurogastrointestinal Encephalomyopathy: Into The Fourth Decade, What We Have Learned So Far

  • 1St George's, University of London, United Kingdom
  • 2University of Cambridge, United Kingdom
  • 3St George's Hospital, United Kingdom

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare metabolic autosomal recessive disease, caused by mutations in the nuclear gene TYMP which encodes the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of the deoxyribonucleosides thymidine and deoxyuridine, and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. Clinically, MNGIE is characterised by gastrointestinal and neurological manifestations, including cachexia, gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, ophthalmoplegia and ptosis. The disease is progressively degenerative and leads to death at an average age of 37.6 years. As with the vast majority of rare diseases, patients with MNGIE face a number of unmet needs related to diagnostic delays, a lack of approved therapies, and non-specific clinical management. We provide here a comprehensive collation of the available knowledge of MNGIE since the disease was first described 42 years ago. This review includes symptomatology, diagnostic procedures and hurdles, in vitro and in vivo disease models that have enhanced our understanding of the disease pathology, and finally experimental therapeutic approaches under development. The ultimate aim of this review is to increase clinical awareness of MNGIE, thereby reducing diagnostic delay and improving patient access to putative treatments under investigation.

Keywords: MNGIE, Thymidine Phosphorylase, mitochondrial disease, rare disease, Deoxyribonucleoside, Mitochondrial neurogastrointestinal encephalomyopathy, TYMP, mitochondrial DNA

Received: 14 Sep 2018; Accepted: 04 Dec 2018.

Edited by:

Enrico Baruffini, Università degli Studi di Parma, Italy

Reviewed by:

Theodora Katsila, University of Patras, Greece
Raffaele Lodi, University of Bologna, Italy  

Copyright: © 2018 Pacitti, Levene, Garone, Nirmalananthan and Bax. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Bridget E. Bax, St George's, University of London, London, SW17 0RE, England, United Kingdom,