Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1).

Massimiliano Filosto,Stefano Cotti Piccinelli,Anna Galvagni,Enrico Baldelli,Filomena Caria,Alessandro Padovani,Serena Gallo Cassarino,Irene Volonghi,Mauro Scarpelli

doi:10.3390/jcm7110389

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE-MTDPS1) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause a loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues, and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Other two MNGIE-type phenotypes have been described so far, which are linked to mutations in POLG and RRM2B genes. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped thymidine phosphorylase therapy) and newer, promising therapies are expected in the near future. Since successful treatment is strictly related to early diagnosis, it is essential that clinicians be warned about the clinical features and diagnostic procedures useful to suspect diagnosis of MNGIE-MTDPS1. The aim of this review is to promote the knowledge of the disease as well as the involved mechanisms and the diagnostic processes in order to reach an early diagnosis.

Highlights

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a rare, devastating, and progressive autosomal recessive mitochondrial disease belonging to the group of defects of inter-genomic communication associated with the depletion and multiple deletions of mitochondrial DNA
The MNGIE type MTDPS1 (OMIM #603041) is caused by mutations in the TYMP gene located on chromosome 22q13.33, which results in the accumulation of the thymidine and deoxyuridine substrates, nucleotide pool imbalance, and mitochondrial DNA (mtDNA) instability with impairment of the mitochondrial genome replication and depletion, multiple deletions, and point mutations [4,5,6]
MNGIE summarizes the main characteristics of mitochondrial diseases: clinical variability, multisystem involvement, and a severe outcome

Summary

Introduction

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a rare, devastating, and progressive autosomal recessive mitochondrial disease belonging to the group of defects of inter-genomic communication associated with the depletion and multiple deletions of mitochondrial DNA (mtDNA). Named Mitochondrial DNA Depletion Syndromes (MTDPS), these diseases are clinically and genetically heterogeneous conditions caused by nuclear gene mutations disrupting deoxy ribonucleotide metabolism, which leads to an imbalance of the mitochondrial nucleotide pool and limited availability of one or more deoxy ribonucleoside triphosphates. Afterward, this results in the instability of the mitochondrial genome and the loss of mtDNA integrity [2,3].

Objectives

Results

Conclusion