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Abstract Details

VCP c.572G>A (p.Arg191Glu) AD Gene Mutation Inclusion Body Myopathy: A Case Report
Neuromuscular and Clinical Neurophysiology (EMG)
P8 - Poster Session 8 (11:45 AM-12:45 PM)
9-012
To describe a rare case of a Valosin-Containing Protein (VCP) gene mutation with its associated autosomal dominant multisystem proteinopathy (IBMPFD) characterized by inclusion body myopathy, early-onset Paget’s disease, and frontotemporal dementia.
Patients with VCP gene mutations exhibit heterogeneous presentations, which may include ALS-like features, emphasizing the genetic overlap between neuromuscular disorders. Key features are progressive muscle weakness, typically presenting in adulthood, along with characteristic early-onset Paget’s disease, potential cognitive impairment or FTD, and cardiomyopathy or ALS phenotype. 

We describe a 43-year-old male with family history of ALS in his paternal uncle and grandmother, presenting with 7 years of progressive lower extremity muscle weakness, starting with left ankle plantarflexion loss. Lab studies are notable for creatine kinase (CK) 477 U/L, Nuclear Bone Scan consistent with Paget's Disease, and EMG showing diffuse, low-amplitude motor unit potentials with fibrillations consistent with a myopathic process. Muscle Biopsy showed chronic myopathic  changes with rimmed vacuoles with ubiquitin and TDP-43 inclusions. Genetic testing showed VCP heterozygous gene mutation in c.572G>A; p.Arg191Glu, consistent with autosomal dominant inclusion body myopathy.
VCP gene mutations result in impaired ubiquitin-proteasome system and autophagy at the cellular level, resulting in cell dysfunction and inclusion body formation. The described mutation in this case was a gain-of-function effect with enhanced ATPase activity, with onset usually 3rd-5th decade and often fatal by age 40s–60s due to cardiorespiratory failure. Weakness can be proximal, distal, scapuloperoneal, or axial. This disorder is associated with autosomal dominant multisystem proteinopathy (IBMPFD) (Inclusion Body Myopathy, early-onset Paget’s disease, and Frontotemporal Dementia). Patients exhibit heterogeneous presentations, mimicking ALS-like features.
  1. Hereditary IBM such as IBMPFD is a consideration with patients with adult-onset myopathy, with mixed proximal/distal weakness, family history, CK elevation, and myopathic process on EMG/nCS. Biopsy shows rimmed vacuoles, genetic testing notable for VCP gene mutations. Monitor such adults for cardiorespiratory complications.
Authors/Disclosures
Sarah Arora, MD
PRESENTER 		Dr. Arora has nothing to disclose.
Katherine Mott, MD Dr. Mott has nothing to disclose.
Archit B. Baskaran, MD (Columbus Plaza) Dr. Baskaran has nothing to disclose.
Betty C. Soliven, MD (University of Chicago) Dr. Soliven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS Pharmacy. The institution of Dr. Soliven has received research support from NIH. The institution of Dr. Soliven has received research support from NIH. The institution of Dr. Soliven has received research support from Alexion. The institution of Dr. Soliven has received research support from Roche/Genentech.
Carlos Lara, MD Dr. Lara has nothing to disclose.
Kourosh Rezania, MD, FAAN (University of Chicago) Dr. Rezania has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Akcea. Dr. Rezania has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnylam.