Abstract
Inclusion body myopathy (IBM) associated with Paget disease of the bone and frontotemporal dementia or IBMPFD is an autosomal dominant degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. We aim to establish a detailed clinical phenotype of VCP disease amongst 35 (28 affected individuals, 7 presymptomatic gene carriers) individuals versus 14 unaffected first-degree relatives in 14 families to establish useful biomarkers for IBMPFD and identify the most meaningful tests for monitoring disease progression in future clinical trials. Comprehensive studies included the Inclusion Body Myositis Functional Rating Scale (IBMFRS) and fatigue severity scale questionairres, strength measurements using the Manual Muscle Test with Medical Research Council (MRC) scales, hand-held dynamometry using the microFET and Biodex dynamometers, 6 minute walk test (6MWT), and pulmonary function studies. Strong correlation was observed between the IBMFRS and measurements of muscle strength with dynamometry and the other functional tests, indicating that it may be utilized in long-term follow-up assessments due to its relative simplicity. This cross-section study represents the most comprehensive evaluation of individuals with VCP disease to date and provides a useful guide for evaluating and possible monitoring of muscle weakness and pulmonary function progression in this unique cohort of individuals.
Highlights
Inclusion Body Myopathy (IBM) associated with Paget’s disease of the bone (PDB) and/or frontotemporal dementia (FTD) or Multisystem Proteinopathy (OMIM 167,320) or more commonly called IBMPFD or valosin-containing protein (VCP) disease, was first reported by Kimonis et al [1]
IBMPFD is caused by dominantly inherited mutations in the valosin-containing protein (VCP) gene mapped to the human chromosomal region 9p13.3–12 and to date, more than 50 disease mutations have been identified in the VCP gene [1,9,10]
As a result of our studies, we found correlations between the Inclusion Body Myositis Functional Rating Scale (IBMFRS) and various tests of muscle strength demonstrating concurrent validity of this questionnaire in this unique population
Summary
Inclusion Body Myopathy (IBM) associated with Paget’s disease of the bone (PDB) and/or frontotemporal dementia (FTD) or Multisystem Proteinopathy (OMIM 167,320) or more commonly called IBMPFD or VCP disease, was first reported by Kimonis et al [1]. VCP disease comprises other less common phenotypes including Amyotrophic Lateral Sclerosis (ALS), Parkinson’s disease, cardiomyopathy, sensory motor axonal neuropathy, and sphincter disturbance [2,3,4,5,6]. IBMPFD is an underdiagnosed disease that has been reported in greater than 100 families worldwide, but is more commonly found in the United States and Europe. Case reports are increasing annually, including reports of unrelated families of Asian, South American and Australian descent [5,7,8]. One of the main functions of the protein is as a chaperone for proteasomal protein degradation and autophagic dysfunction leading to protein aggregation [11,12,13,14,15]
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