Abstract Details

Title Description of clinical symptoms of a large international cohort of patients with valosin-containing-protein related disease

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S12 - Interventional/Observational Studies of Neuromuscular Diseases (4:40 PM-4:48 PM)

Poster/Presentation
Number 005

Background VCP gene mutations are associated with several disorders such as hereditary inclusion body myopathy, Paget’s disease of bone (PDB), polyneuropathy, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis. There is huge heterogeneity in the phenotypes reported in different patient series.

Objective

To describe clinic and genetic features of an international cohort of patients with valosin-containing-protein (VCP) related disease.

Design/Methods

An ongoing multi-centric observational retrospective study. Demographic, clinical and genetic data were collected from patients with a confirmed pathogenic mutation in VCP.

Results Sixty patients seen at 6 neuromuscular centres were included. The most common mutation was p.Arg155His (31,7%). The mean age of symptoms onset was 44.5±10.5 years. Muscle weakness was the first manifestation in 93.2% of the patients, PBD in 5.1% and polyneuropathy in 1 patient. There was large heterogeneity in the muscles that were affected at disease onset, with proximal and distal muscles of the lower limbs being the most commonly involved. Fifty-one percent of the patients developed global muscle weakness and 30.3% lost ambulation after a mean disease duration of 5.6±3.5 and 9.7±8 years respectively. Cognitive problems were reported in 15 patients of which 9 fulfilled FTD diagnostic criteria. Respiratory symptoms were reported by 43.3% and 9 patients (15%) required non-invasive ventilation after a median of 8 years (range 3-29) from disease onset. Cardiac involvement was only seen in 6%. Additional clinical features were: PDB (28%), drop head (12%), polyneuropathy (13%) and urine incontinence (25%). The most common EMG finding was a myopathic pattern (69,2%) and 70% of the muscle biopsies showed rimmed vacuoles.

Conclusions

Our study shows that VCP-related disease is an adult-onset progressive multisystemic disorder that leads to severe disability. The results of this study will shed light on the most common symptoms and will be helpful to provide tailored care for this group of patients.

Authors/Disclosures
Marta Caballero-Ávila, MD (Hospital de la Santa Creiu i Sant Pau) PRESENTER	Marta Caballero-Ávila has nothing to disclose.
Chiseko Ikenaga, MD, PhD (Johns Hopkins University School of Medicine)	Dr. Ikenaga has nothing to disclose.
Chiara Marini-Bettolo (Newcastle University)	Chiara Marini-Bettolo has nothing to disclose.
Michela Guglieri	The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne. The institution of Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NS Pharma. Michela Guglieri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. The institution of Michela Guglieri has received research support from EC - H2020. The institution of Michela Guglieri has received research support from Duchenne UK. The institution of Michela Guglieri has received research support from Sarepta. The institution of Michela Guglieri has received research support from DMD Research Fund.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Pascal Lafort	No disclosure on file
Tanya Stojkovic	Tanya Stojkovic has nothing to disclose.
Conrad Weihl, MD, PhD (Washington University in St. Louis)	Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Casma therapeutics. Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata. Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Weihl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acceleron. Dr. Weihl has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Wilson Elser Moskowitz Edelman & Dicker LLP.
Jordi Diaz-Manera (Newcastle University)	No disclosure on file