Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network

J Inherit Metab Dis. 2021 Mar;44(2):376-387. doi: 10.1002/jimd.12300. Epub 2020 Sep 8.

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.

Keywords: TYMP; consensus conference; enzyme replacement; mitochondrial disease; mitochondrial neurogastrointestinal encephalomyopathy; thymidine phosphorylase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Consensus
  • DNA, Mitochondrial / genetics
  • Gastrointestinal Diseases / diagnosis*
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / therapy*
  • Humans
  • International Cooperation
  • Mitochondrial Encephalomyopathies / diagnosis*
  • Mitochondrial Encephalomyopathies / genetics
  • Mitochondrial Encephalomyopathies / metabolism
  • Mitochondrial Encephalomyopathies / therapy*
  • Mutation
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism

Substances

  • DNA, Mitochondrial
  • Thymidine Phosphorylase