Donáth Judit, Speer Gábor, Kósa János P, Árvai Kristóf, Balla Bernadett, Juhász Péter, Lakatos Péter, Poór Gyula
Judit Donáth, National Institute of Rheumatology and Physiotherapy, Frankel-Leó u. 38-40, Budapest, H-1023, Hungary,
Croat Med J. 2015 Apr;56(2):145-51. doi: 10.3325/cmj.2015.56.145.
Juvenile Paget's disease (JPD) is a rare autosomal-recessive condition. It is diagnosed in young children and characterized by a generalized increase in bone turnover, bone pain, and skeletal deformity. Our patient was diagnosed after a pathological fracture when she was 11 years old. When we first examined her at the age of 30 she had bone pain and deformity in both the femur and tibia. Serum alkaline phosphatase (ALP) level, radiology, bone scintigraphy, and densitometry were monitored. Next generation sequencing (NGS) technology, namely semiconductor sequencing, was used to determine the genetic background of JPD. Seven target genes and regions were selected and analyzed after literature review (TM7SF4, SQSTM1, TNFRSF11A, TNFRSF11B, OPTN, CSF1, VCP). No clear pathogenic mutation was found, but we detected missense polymorphisms in CSF1 and TM7SF4 genes. After treatment with zoledronic acid, infusion bone pain and ALP level decreased. We can conclude that intravenous zoledronic acid therapy is effective and safe for suppressing bone turnover and improving symptoms in JPD, but the long-term effects on clinical outcomes are unclear. Our findings also suggest that NGS may help explore the pathogenesis and aid the diagnosis of JPD.
青少年佩吉特病（JPD）是一种罕见的常染色体隐性疾病。它在幼儿期被诊断出来，其特征是骨转换普遍增加、骨痛和骨骼畸形。我们的患者在11岁时因病理性骨折被诊断出来。当我们在她30岁时首次检查她时，她的股骨和胫骨都有骨痛和畸形。监测了血清碱性磷酸酶（ALP）水平、放射学、骨闪烁显像和骨密度测定。使用下一代测序（NGS）技术，即半导体测序，来确定JPD的遗传背景。在文献综述后选择并分析了七个靶基因和区域（TM7SF4、SQSTM1、TNFRSF11A、TNFRSF11B、OPTN、CSF1、VCP）。未发现明确的致病突变，但我们在CSF1和TM7SF4基因中检测到错义多态性。在用唑来膦酸治疗后，输注性骨痛和ALP水平下降。我们可以得出结论，静脉注射唑来膦酸治疗对于抑制JPD中的骨转换和改善症状是有效且安全的，但对临床结局的长期影响尚不清楚。我们的研究结果还表明，NGS可能有助于探索JPD的发病机制并辅助其诊断。
