G.P.39

X-linked myotubular myopathy (XLMTM) is the most severe form of centronuclear myopathy affecting approximately 1 in 50,000 male newborns. Phenotype varies from mild to severe. Several cases of affected females are also reported.presently, there is no effective treatment for the muscle weakness in XLMTM patients. Several promising strategies, including protein replacement therapy and gene therapy, are currently in development.due to the variability of the phenotype, it is important to determine the best outcome measure to assess the efficacy of potential therapies and the prognostic factors for the disease. We present here a prospective study of the pathophysiology of XLMTM to characterize the disease course by using standardized evaluations. A total of 60 patients with XLMTM, male or symptomatic female of any age, are planned to be enrolled in North America and Europe. Visit frequency and assessments are adjusted to age, ambulatory and respiratory status. Evaluations include standard liver ultrasound, clinical exam, ophthalmoplegia assessment, pulmonary function tests, strength and motor function assessment by using upper limb-specific devices and common scales, six-minute walk test, activity monitoring using the Actimyo device and quality of life assessment. Blood samples are collected to test immunization against AAV and to quantify MTM1 protein level. Urinary creatinine excretion is assessed every 6 months. Data from the patients’ usual follow-up care are collected from their medical files including psychomotor development, respiratory, cardiac, hematology kidney and liver functions, feeding status and ophthalmologic assessment. According to the weakness of the patient, if needed, the assessments by a physiotherapist can be performed at home. The obtained data will help to characterize the course of disease and the disease spectrum of XLMTM and may help to empower future therapeutic studies as well as to eventually substitute for placebo groups.