Pacitti, D; Levene, M; Garone, C; Nirmalananthan, N; Bax, BE
(2018)
Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far.
Front Genet, 9.
p. 669.
ISSN 1664-8021
https://doi.org/10.3389/fgene.2018.00669
SGUL Authors: Bax, Bridget Elizabeth Levene, Michelle Pacitti, Dario
Abstract
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 characterized 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.
Item Type: |
Article
|
Additional Information: |
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 http://creativecommons.org/licenses/by/4.0/). 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. |
Keywords: |
MNGIE, TYMP, deoxyribonucleoside, mitochondrial DNA, mitochondrial disease, mitochondrial neurogastrointestinal encephalomyopathy, rare disease, thymidine phosphorylase, MNGIE, thymidine phosphorylase, mitochondrial disease, rare disease, deoxyribonucleoside, TYMP, mitochondrial DNA, mitochondrial neurogastrointestinal encephalomyopathy |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Front Genet |
ISSN: |
1664-8021 |
Language: |
eng |
Dates: |
Date | Event |
---|
21 December 2018 | Published | 4 December 2018 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
30627136 |
Web of Science ID: |
WOS:000454110000001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/110444 |
Publisher's version: |
https://doi.org/10.3389/fgene.2018.00669 |
Statistics
Item downloaded times since 23 Jan 2019.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |