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

Antonio Siniscalchi, Carla Giordano, Laura Ludovica Gramegna, Michelle Levene, Raffaele Lodi, Hanna Mandel, Maria Cristina Morelli, Olimpia Musumeci, Alessia Pugliese, Mauro Scarpelli, Maria Teresa Dotti, Antonella Spinazzola, Galit Tal, Javier Torres-Torronteras, Luca Vignatelli, Irina Zaidman, Heinz Zoller, Rita Rinaldi, Massimo Zeviani, Massimiliano Filosto, Francesco Nonino, Roberto De Giorgio, Elisa Boschetti, Valerio Carelli, Loris Pironi, Anna Accarino, Giovanna Cenacchi, Roberto D'Alessandro, Michio Hirano, Ramon Martí, Antonio Daniele Pinna, Elisa Baldin, Bridget Elizabeth Bax, Alessio Bolletta, Riccardo Bolletta, Matteo Cescon, Roberto D'Angelo

Journal: Journal of inherited metabolic disease 2021;44(2):376-387

PMID: 32898308

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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.

Address: Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.; Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.; Clinical Nutrition and Metabolism Unit and Center for Chronic Intestinal Failure, Department of Digestive System, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.; Digestive System Research Unit, University Hospital Vall d'Hebron / Centro de Investigación Biomédica en Red de Enfermeda des Hepáticas y Digestivas (CIBEREHD); Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.; Center for Neuromuscular Diseases, Unit of Neurology, Azienda Socio Sanitaria Territoriale degli Spedali Civili and University of Brescia, Brescia, Italy.; Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Autonomous University of Barcelona, Barcelona, Spain.; University of Bologna, St. Orsola-Malpighi Hospital, Bologna, Italy.; Institute of Molecular and Clinical Sciences, St George's University of London, London, UK.; Mitochondrial Patients, Mitocon ONLUS, Rome, Italy.; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; General Surgery and Transplant Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Interaziendale Metropolitana (NeuroMet), - Neurologia AOU S.Orsola-Malpighi, Bologna, Italy.; Neurological and Metabolic Diseases Clinic, Siena Hospital, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.; Department of Radiological, Oncological and Pathological Sciences, Sapienza, University of Rome, Umberto I Policlinic, Rome, Italy.; Institute of Human Genetics and Inherited Metabolic Disorders, Galilee Medical Center, Nahariya, Israel.; Department for Care of Organ Failures and Transplants, Internal Medicine for the Treatment of Severe Organ Failures, St. Orsola-Malpighi Hospital, Bologna, Italy.; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.; Neurology Unit, Department of Neuroscience, Azienda Ospedaliero Universitaria Integrata Verona, Verona, Italy.; Anaesthesiology Intensive Care and Transplantation Unit, St. Orsola-Malpighi Hospital, Bologna, Italy.; Department of Clinical Movement Neurosciences, Royal Free Campus, University College of London, Queen Square Institute of Neurology, London, UK.; Metabolic Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.; Department of Bone Marrow Transplantation, Hadassah University Medical Center, Jerusalem, Israel.; Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.; Department of Neurosciences, Veneto Institute of Molecular Medicine, University of Padova, Padova, Italy.

DOI: 10.1002/jimd.12300

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MeSH Terms: Consensus, DNA, Mitochondrial, Gastrointestinal Diseases, Humans, International Cooperation, Mitochondrial Encephalomyopathies, Mutation, Thymidine Phosphorylase