Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray,
radionuclide bone scan, and serum levels of
alkaline phosphatase (ALP),
procollagen type 1 N-terminal propeptide (P1NP), and β-carboxy-terminal cross-linked telopeptide of
type 1 collagen (β-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of
intravenous infusion of
zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the
valosin-containing protein (VCP). The patient only exhibited bone
pain as the initial manifestation with vertebral
compression fracture and extremely elevated ALP, P1NP, and β-CTX levels; she had no inclusion body
myopathy and
frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone
pain and a marked decline in ALP, P1NP, and β-CTX levels were observed after
zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had
myopathy,
frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to
zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.