Columbres Rod Carlo Agram, Din Sarosh, Gibbs Liliane, Kimonis Virginia
Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA.
College of Osteopathic Medicine, William Carey University, Hattiesburg, MS, USA.
Sci Rep. 2024 Mar 11;14(1):5917. doi: 10.1038/s41598-024-54526-7.
Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget's disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.
多系统蛋白病1(MSP1)是一种罕见的遗传性疾病,由含缬酪肽蛋白(VCP)基因突变引起,具有包涵体肌病(IBM)、额颞叶痴呆(FTD)和骨佩吉特病(PDB)的临床特征。我们对12例(6例女性,6例男性)确诊为VCP基因突变的患者进行了骨扫描成像,其中6例(50%)仅有肌病,4例(33%)同时患有PDB和肌病,2例(15%)为症状前携带者。我们旨在对已确诊个体中的PDB进行特征描述,并潜在地在肌病组和症状前组中识别出PDB。有趣的是,两名先前未确诊PDB的患者在骨扫描及后续X光片成像中出现了阳性诊断结果。在患有PDB的个体中,受累骨骼放射性示踪剂摄取增加,其分布具有典型性,如在传统PDB以及其他MSP1队列中所报道的那样,即胸椎和肋骨(75%)、骨盆(75%)、肩部(75%)和颅骨(15%)。总体而言,我们表明定期进行的锝-99m骨扫描是对有PDB风险的MSP1相关VCP变异患者进行筛查的敏感工具。然而,诊断确认应结合临床病史、生化分析和骨骼X光片,以促进早期治疗并预防并发症,同时要认识到其特异性有限。