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Bax. J Transl Genet Genom 2020;4:1-16 Journal of Translational
DOI: 10.20517/jtgg.2020.08 Genetics and Genomics

Review Open Access

Mitochondrial neurogastrointestinal
encephalomyopathy: approaches to diagnosis and

treatment

Bridget E. Bax

Institute of Molecular and Clinical Sciences, St. George’s University of London, London, SW17 0RE, UK.

Correspondence to: Dr. Bridget E. Bax, Institute of Molecular and Clinical Sciences, St George’s University of London, Cranmer
Terrace, London, SW17 0RE, United Kingdom. E-mail: bebax@sgul.ac.uk
How to cite this article: Bax BE. Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and
treatment. J Transl Genet Genom 2020;4:1-16. http://dx.doi.org/10.20517/jtgg.2020.08
Received: 1 Feb 2020 First Decision: 24 Feb 2020 Revised: 24 Feb 2020 Accepted: 27 Feb 2020 Published: 30 Mar 2020

Science Editor: Andrea L. Gropman Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease caused by mutations
in TYMP, the gene encoding for the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a
systemic accumulation of thymidine and 2’-deoxyuridine and ultimately mitochondrial failure due to a progressive
acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. MNGIE is characterised
by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy.
The disease is progressively degenerative and leads to death at an average age of 37.6 years. Patients invariably
encounter misdiagnoses, diagnostic delays, and non-specific clinical management. Despite its rarity, MNGIE has
invoked much interest in the development of therapeutic strategies, mainly because it is one of the few mitochondrial
disorders where the molecular abnormality is metabolically and physically accessible to manipulation. This review
provides a résumé of the current diagnosis and treatment approaches and aims to increase the clinical awareness
of MNGIE and thereby facilitate early diagnosis and timely access to treatments, before the development of
untreatable and irreversible organ damage.

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Keywords: Mitochondrial neurogastrointestinal encephalomyopathy, MNGIE, thymidine phosphorylase, TYMP
mitochondrial DNA, mitochondrial disease

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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