Abstract Details

VCP pathogenic variants cause MSP which manifests with inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS)/ frontotemporal dementia, and Paget disease of bone (PDB), in isolation or in combination. The myopathy mean age of onset is 40-45 years; the previously reported youngest patient with VCP-IBM was 18-year-old.

Review of clinical and laboratory findings.

The patient manifested at age 16 with asymmetric distal lower limb weakness, which extended to proximal four limb and axial muscles, leading to loss of ambulation at age 35. He carried the diagnosis of non-5q spinal muscular atrophy, based on “neurogenic” electromyography (EMG) findings. Neurological examination at age 39 showed mild-to-moderate weakness (Medical Research Council, MRC, grade 3-4) of neck and upper limb muscles, and severe mildly asymmetric lower limb weakness (MRC grade 1-2) with leg muscle plegia but partially spared toe flexors, diffuse muscle atrophy and scapular winging. Creatine kinase value was normal. Alkaline phosphatase was elevated at 350 U/L (normal 50-136 U/L) since age 36.  EMG detected mixed low amplitude, short duration and high amplitude, long duration motor unit potentials. Bone survey demonstrated changes of PDB in skull, pelvis, and long bones. Genetic test identified a novel heterozygous VCP variant of unknown significance affecting a highly conserved amino acid in the N-terminal of the protein, a substrate binding domain (c.467G>T, p.Gly156Val). Biopsy of extensor carpi radialis showed features of IBM, which, in combination with the newly diagnosed PDB, supported the VCP variant pathogenicity.

To our knowledge, this is the youngest reported patient with VCP-MSP. VCP-MSP is not only a disease of adulthood but can have a pediatric onset and should be considered in differential diagnosis of neuromuscular weakness in the pediatric population.