A Natural History Study of VCP Associated Vacuolar Myopathy in a Patient with the Common R155H Mutation

Abstract

Background: IBMPFD (Inclusion Body Myopathy associated with Paget disease of the bone and Frontotemporal Dementia) is an autosomal dominant inherited disease caused by VCP gene mutations. Very little natural history data exists on this disease. We report a patient with a significant family history of IBMPFD associated with the common R155H mutation in the VCP gene. Objective: This study will address the lack of long-term data for muscle strength, and respiratory function in IBMPFD. The hypothesis is that detailed analysis in a single patient will provide meaningful natural history data in IBMPFD, a progressive neurodegenerative disease. Method: Regression analysis was performed across multiple parameters related to myopathy including dynamometry, MRC scale, IBM functional rating scale, pulmonary function studies and sleep quality. Results: Measurements of this patient highlight progressive generalized weakness in proximal and distal regions, decline in pulmonary function, and asymmetrical strength differences of the upper extremities. Measurements over five years revealed an overall deterioration with a slope of -1.13 and R2 value of 0.77. Conclusion: This unique data derived from long-term evaluations in a patient provides the first report of the rate of progression of muscle weakness and pulmonary function deterioration in VCP associated inclusion body myopathy.