Objective: Valosin-containing protein (VCP) mutation causes a multiorgan disease characterized by inclusion body myopathy, Paget disease and frontotemporal dementia, more rarely by Charcot-Marie-Tooth disease type 2, hereditary spastic paraplegia and Parkinson’s Disease (PD) [1].

Background: Here we present the case of a 40 years-old man with a progressive onset of fasciculations and weakness of the legs that leads to gait difficulties. Neurological examination showed a mild reduction of bilateral legs strength, normal sensitivity and bilaterally reduced ankle jerk. The electroneurography revealed a motor symmetric demyelinating neuropathy of lower limbs sparing the sensitive branches and the upper arms. Cerebrospinal fluid analysis revealed the presence of albumin-cytological dissociation (proteins 112 mg/dl; <5 cells/mm3).

Method: Accordingly, a diagnosis of atypical definite chronic inflammatory demyelinating polyneuropathy (CIDP) was made [2]. After an unsuccessful steroid therapy, intravenous immunoglobulin (IVIg) therapy was started with moderate benefit. A muscular biopsy confirmed a neurogenic chronic pattern without myopathic signs. Despite the monthly IVIg administration, the clinical picture worsened over the years with diffuse muscular atrophy and hyposthenia and a progressive worsening of the demyelinating polyneuropathy at lower limbs with sensorial involvement and conduction blocks that after 14 years involved the upper limbs as well. The subsequent CSF analyses confirmed an albumin-cytological dissociation. At 49 years old, a parkinsonian syndrome appeared: he presented with hypomimia, bilateral bradykinesia, minimal resting tremor and plastic rigidity. A 123I-FP-CIT SPECT confirmed the depletion of dopaminergic pathways supporting the diagnosis of clinically established Parkinson’s Disease. Dopaminergic therapy was started with good motor clinical benefit. Over the years, a prominent assial involvement appeared with marked camptocormia and Pisa syndrome leading to the need of a wheelchair at 57 years.

Results: To further investigate this complex neurological case, a Whole Exome Sequencing examination was performed, showing a novel mutation in the VCP gene: c.1106T>C.

Conclusion: Here, we described an unusual case of a patient carrying a novel VCP mutation presenting with CIDP and early-onset PD broadening the clinical spectrum of possible VCP gene mutations phenotypes.

References: [1] C. C. Weihl, A. Pestronk, and V. E. Kimonis, “Valosin-containing protein disease: Inclusion body myopathy with Paget’s disease of the bone and fronto-temporal dementia,” Neuromuscular Disorders, vol. 19, no. 5, pp. 308–315, May 2009, doi: 10.1016/j.nmd.2009.01.009.
[2] R. A. C. Hughes et al., “European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society,” Eur J Neurol, vol. 13, no. 4, pp. 326–332, Apr. 2006, doi: 10.1111/j.1468-1331.2006.01278

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-and-chronic-inflammatory-demyelinating-polyneuropathy-broadening-the-clinical-spectrum-of-vcp-mutations/