Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a very rare autosomal recessive disease leading to marked mitochondrial DNA (mtDNA) maintenance abnormalities. Clinical manifestations include intestinal (weight loss, cachexia, diarrhoea, intestinal pseudo-obtruction) and neurological (polineuropathy, ptosis, ophtalmoparesis, leukoencephalopathy) symptoms and signs. Due to its rarity and non-specific symptoms, MNGIE is often misdiagnosed. To correct the nucleoside imbalance responsible of mtDNA maintenance abnormalities, several permanent enzyme-replacement treatments are available, among which hematopoietic stem cell transplantation (HSCT) and liver transplantation. Due to the extreme rarity of the condition, it is unlikely that evidence from controlled trials will ever be available; therefore, consistency in research methods on MNGIE is of pivotal importance, particularly in defining efficacy and safety outcomes. A core outcome set (COS) is therefore warranted to adopt consistent, clinically meaningful and useful effect measures for MNGIE. The COS-MNGIE project is promoted by the MITOCON advocacy group for people affected by mitochondrial diseases. COS was developed according to the Core Outcome Measures in Effectiveness Trials (COMET) Initiative standards and recommendations by means of a mixed-method approach including scoping literature review, a global survey among people with MNGIE and a modified Delphi method among healthcare professionals to select, score and summarize the outcomes. The final COS was presented and agreed during a final meeting involving the key interest-holders. Each outcome is described unambiguously together with the recommended timing of assessment. The outcome describing quality of life for people with MNGIE has been developed by adapting the SAVEQoL instrument to the quality of life domains elicited from a sample of patients through a global survey.
ContributorsFrancesco Nonino (PI), Claudia De Santis, Elisa Baldin, Luca Vignatelli, martino Schettino, Flavia Baccari UO di Epidemiologia e Statistica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Rita Rinaldi, UOC Interaziendale Metropolitana (NeuroMet), Neurologia AOU S.Orsola-Malpighi, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Serena Massucci, MITOCON ONLUS, Rome, Italy
Michio Hirano, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
Matteo Cescon, Dipartimento di Chirurgia Generale e Trapianti - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Carolina Malagelada, Digestive System Research Unit, University Hospital Vall d'Hebrón - 08035 Barcelona, Spain
Ramon Martí, Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras (CI-BERER), Autonomous University of Barcelona, Barcelona, Spain
Maria Cristina Morelli, UOC Medicina Interna per il trattamento delle gravi insufficienze d'organo, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Agathe Roubertie, Departement de Neuropediatrie, CHU Gui de Chauliac, Institut des Neurosciences de Montpellier, Montpellier, France
Katia Mattarozzi, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) – Università degli Studi di Bologna, Bologna, Italy
Valerio Carelli, IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
Roberto De Giorgio, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
Silvano Pioli, person with MNGIE (deceased)
Disease Category: Neurology
Disease Name: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Age Range: 18 - 50
Sex: Either
Nature of Intervention: Drug, Procedure
- Charities
- Clinical experts
- Conference participants
- Consumers (patients)
- Epidemiologists
- Methodologists
- Patient/ support group representatives
- Researchers
- Statisticians
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Literature review
- Semi structured discussion
- Survey
The COS-MNGIE project was conducted between February 13, 2023 and July 11, 2025 and comprised four sequential phases: (1) project scoping, including protocol development and registration with the involvement of the SAG; (2) information sourcing, consisting of a rapid literature review and a global online survey involving people with MNGIE and supervised by the SAG; (3) consensus process, involving two Delphi rounds among clinicians and MNGIE experts; and (4) COS finalization, including a final online consensus meeting with people with MNGIE, caregivers, clinicians, and SAG members, leading to the development of the final COS. It was promoted by MITOCON, Insieme per lo studio e la cura delle malattie mitocondriali Odv, the Italian advocacy group on mitochondrial diseases (https://www.mitocon.it/) and developed according to the Core Outcome Measures in Effectiveness Trials (COMET) Initiative standards and recommendations. The protocol was developed according to the COS-STAP Stetement and the outcome set is reported according to the COS-STAR standards. A Scientific Advisory Group (SAG) was mandated by MITOCON to oversee the whole development process. It included clinicians with expertise in MNGIE, one biochemist, a representative of the MITOCON advocacy group, one methodologist, and a person with MNGIE. The SAG gave active input in the stages of project scoping, information sourcing and COS finalization. Organisational aspects and the update of the rapid literature review were performed by a Project Management Group within the Cochrane Review Group Multiple Sclerosis and Rare Diseases of the SNC, based at the Unit of Epidemiology and Statistics of the IRCCS Institute of Neurological Sciences of Bologna, Bologna (Italy).