The purpose of this protocol is to report the methodology for the development of a Core Outcome Set (COS) for the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). A COS represents the minimum that should be measured in a clinical trial for a particular condition. The aim of the COLT-MNGIE project is to develop a COS to be used in research on the efficacy, safety and value of liver transplantation for MNGIE and other permanent enzyme-replacement treatments. COS will be developed according to the Core Outcome Measures in Effectiveness Trials (COMET) Initiative standards and recommendations. The COLT-MNGIE project is promoted by MITOCON (https://www.mitocon.it/), the Italian advocacy group on mitochondrial diseases, and it will involve healthcare professionals (neurologists, paediatric neurologists, gastroenterologists, transplant surgeons, post-surgical ICU specialists, nutritionists), biochemists and other researchers/professionals, persons with MNGIE, their care givers and methodologists.