Clinical and Electrophysiological Presentation of a Patient with Multisystem Proteinopathy Associated with Valosin-Containing Protein Mutation (P5-8.005)

Abstract

<h3>Objective:</h3> Present a rare case of multisystem proteinopathy (MSP) of apparently unrelated multisystem conditions caused by mutation in valosin-containing protein (VCP). <h3>Background:</h3> Multisystem proteinopathy (MSP) is a dominantly inherited disorder causing bone, muscle, central and peripheral nervous systems disease. Mutations within the gene encoding valosin-containing protein (VCP) cause MSP. Such mutations present with a vast phenotypical variability and are associated with inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. We present a case of MSP caused by c.464G&gt;A, p. arg155his mutation in VCP. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 65-year-old woman presented with proximal muscle weakness and unsteady gait. The symptoms started four years ago when she experienced progressive weakness of the upper and lower extremities leading to recurrent falls. She has no family history of similar symptoms or genetic disease. Examination revealed dropped head, scapular winging, inability to raise the arms above her shoulders, hand weakness, and bilateral foot drop. Her gait was unsteady with a mix of waddling and steppage. Creatine kinase and alkaline phosphatase levels were normal. MRI of spine revealed mild degenerative disc disease from C4–C7 and disc bulges at L3–L4 through L5–S1. The nerve conduction studies showed mixed myopathic and neurogenic changes with ongoing denervation in cervical and lumbar segments suggestive of motor neuronopathy. Genetic testing was remarkable for a heterozygous pathogenic mutation in VCP (c.464G&gt;A, p. arg155his). <h3>Conclusions:</h3> This case highlights the need to consider MSP in patients with a complex neurological presentation and combined myopathic and neurogenic electrodiagnostic findings. The absence of MSP-related symptoms in the patient’s family may indicate the variable severity associated with the same VCP mutation, interaction with environmental factors as well as presence of genetic modifiers.. <b>Disclosure:</b> Mr. Halber has nothing to disclose. Sabrina Bulancea has nothing to disclose. Dr. Treidler has nothing to disclose.