MEHMO Natural History and Biomarkers

Study Description: This is a prospective natural history study of individuals who have MEHMO syndrome or eIF2-pathway related conditions, or who are carriers of EIF2S3-related conditions to generate hypotheses for further understanding of disease pathophysiology, diagnosis, prognosis, management, and treatment. The protocol aims to enroll and follow affected or carrier individuals longitudinally to establish a repository of concurrent evaluations and biomaterials, as well as to enroll unaffected individuals for collection of informative comparable data and samples. Objectives: Primary Objective: Characterize the presentation of MEHMO syndrome and eIF2 pathway related conditions. Secondary Objectives: 1. Identify disease-reflective fluid biomarkers 2. Develop a disease severity rating scale or classification algorithm 3. Assess tolerability and feasibility of study evaluations 4. Establish a repository of participant data and samples for future research Endpoints: Primary Endpoint: Frequency and time-to-event of signs and symptoms. Secondary Endpoints: 1. Mean difference of candidate fluid biomarkers level in affected versus carrier versus unaffected individuals 2. Correlation of rating scale or classification algorithm to age, genotype, or other variables 3. Frequency of completed evaluations and reasons for noncompletion