Abdoalsadig Eiman, Hamid Merwa, Peck Allison, Johar Leepakshi, Kimonis Virginia
Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California Irvine, Lab and FEDEX: Hewitt Hall, Rm 2038, Health Sciences Rd., Irvine, CA, 92697, USA.
Yale School of Public Health, New Haven, CT, USA.
Orphanet J Rare Dis. 2025 Apr 15;20(1):178. doi: 10.1186/s13023-025-03567-w.
VCP disease, also known as multisystem proteinopathy, is a rare, autosomal dominant, adult-onset, neuromuscular disease that is caused by variants in the valosin-containing protein (VCP) gene. VCP disease may exhibit one or more of the following primary features: inclusion body myopathy, Paget's disease of bone (PDB), Frontotemporal dementia, and amyotrophic lateral sclerosis. Due to its progressive nature, death normally occurs in their sixties due to respiratory and cardiac failure. The purpose of this study is to utilize the Cure VCP Disease patient registry hosted by the Coordination of Rare Diseases at Sanford (CoRDS) to conduct a prospective natural history study.
Seventy-nine participants enrolled in the patient registry and answered demographic, VCP variant type, Patient-reported outcome measures (PROMs), and quality of life (QOL) questionnaires over the course of 3 years. We additionally investigated if any sex differences existed and if genotype-phenotype correlations affected the rate of progression of the varying clinical manifestations.
Overall, participants' mobility declined significantly as the disease progressed. Participants reported a 0.6% decline in upper extremity function, 1.2% decline in lower extremity function, and 0.3% decline in cognitive function per year of age. Furthermore, participants reported a 1.6% decline in upper and lower extremity function and a 0.1% decline in cognitive function per year of disease duration. The highest PROMs correlations were noted between overall health and lower extremity function, upper extremity function, fatigue, and the ability to perform vigorous activities. Genotype-phenotype correlations revealed no significant differences except for the absence of PDB in the p.Arg159Cys group.
The VCP CoRDS Registry was found to be a valuable tool for monitoring the QOL in patients with VCP disease and capturing patient perspectives for future clinical trials.
VCP病,也称为多系统蛋白病,是一种罕见的常染色体显性成人发病的神经肌肉疾病,由含缬酪肽蛋白(VCP)基因的变异引起。VCP病可能表现出以下一种或多种主要特征:包涵体肌病、骨佩吉特病(PDB)、额颞叶痴呆和肌萎缩侧索硬化。由于其进行性本质,患者通常在60多岁时因呼吸和心力衰竭而死亡。本研究的目的是利用由桑福德罕见病协调中心(CoRDS)主办的治愈VCP病患者登记处进行一项前瞻性自然史研究。
79名参与者登记加入患者登记处,并在3年期间回答了人口统计学、VCP变异类型、患者报告结局测量(PROMs)和生活质量(QOL)问卷。我们还调查了是否存在任何性别差异,以及基因型-表型相关性是否影响不同临床表现的进展速度。
总体而言,随着疾病进展,参与者的活动能力显著下降。参与者报告,每年年龄增长导致上肢功能下降0.6%,下肢功能下降1.2%,认知功能下降0.3%。此外,参与者报告,疾病持续时间每增加一年,上下肢功能下降1.6%,认知功能下降0.1%。在总体健康与下肢功能、上肢功能、疲劳以及进行剧烈活动的能力之间,观察到PROMs的相关性最高。基因型-表型相关性显示,除了携带p.Arg159Cys变异的组中不存在PDB外,没有显著差异。
发现VCP CoRDS登记处是监测VCP病患者生活质量以及获取患者观点以用于未来临床试验的宝贵工具。