常染色体隐性遗传性青少年型帕金森病临床特点及疗效评价

doi:10.3969/j.issn.1672-6731.2021.06.005

摘要/Abstract

摘要：

目的报道1例常染色体隐性遗传性青少年型帕金森病（AR-JP）患者，总结其临床表现、影像学和基因检测结果、治疗与转归。方法与结果 女性患者，27岁，临床表现为肢体僵硬、不灵活以及四肢不自主抖动，其二妹有类似症状。¹⁸F-DOPA PET显示双侧纹状体后部多巴胺代谢降低。基因检测显示，患者存在PRKN基因外显子12 c.1321T > C（p.Cys441Arg）错义突变以及LRRK2-41（MUT）G2019S和SNCA-2（MUT）A30P杂合缺失，为致病性变异。最终诊断为AR-JP，予多巴丝肼治疗，症状明显减轻但出现异动症，多巴丝肼减量并联合应用苯海索和普洛卡索，症状缓解，未见异动症和"开关"现象。结论 AR-JP系PRKN基因复合杂合突变所致，左旋多巴制剂治疗有效，与苯海索和普洛卡索联用效果更佳，可减少异动症和"开关"现象。AR-JP早期诊断、及时治疗，对患者预后意义重大。

关键词: 帕金森病, 基因, 隐性, 染色体障碍, 帕金森病相关蛋白质类, 正电子发射断层显像术, 青少年

Abstract:

Objective To report one case of autosomal recessive juvenile-onset Parkinson's diseased (AR -JP), and summarize its clinical manifestations, imaging and genetic testing results, treatment and outcome. Methods and Results A female patient, 27 years old, clinically manifested as stiffness, inflexibility and involuntary shaking of limbs. Her second sister had similar symptoms. ¹⁸F-DOPA PET showed decreased dopamine metabolism in the posterior striatum of both sides. Genetic testing showed that the patient had a heterozygous deletion of the ^PRKN gene exon 12 c.1321T > C (p.Cys441Arg) and ^LRRK2-41 (^MUT) G2019S and ^SNCA-2 (^MUT) A30P mutations, which were caused by disease variants. The final diagnosis was AR -JP, and she was treated with dopasrazide. The symptoms were significantly reduced but dyskinesia occurred. The dose of dopasrazide was reduced and the combination of trihexyphenidyl and procassone was used. The symptoms were relieved. No dyskinesias and "switching phenomenon" were seen. Conclusions AR-JP is caused by a compound heterozygous mutation in the ^PRKN gene. The treatment of levodopa is effective, and the combination of diphenhexol and procassol has a better effect, and can reduce dyskinesia and "switching". Early diagnosis and timely treatment of AR-JP are of great significance to the prognosis of patients.

Key words: Parkinson disease, Genes, recessive, Chromosome disorders, Parkinson disease associated proteins, Positron-emission tomography, Adolescent

张悦, 张成, 李娟, 吴竞婧, 林东. 常染色体隐性遗传性青少年型帕金森病临床特点及疗效评价[J]. 中国现代神经疾病杂志, 2021, 21(6): 454-459.

ZHANG Yue, ZHANG Cheng, LI Juan, WU Jing-jing, LIN Dong. Clinical characteristics and therapeutic evaluation of autosomal recessive juvenil-onset Parkinson's disease[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(6): 454-459.

http://journal11.magtechjournal.com/cjcnn/CN/Y2021/V21/I6/454

参考文献

[1] Ge FF, Li YF, Sun HB. A case of Parkin-related adolescent Parkinson's disease[J]. Zhongguo Shen Jing Mian Yi Xue He Shen Jing Bing Xue Za Zhi, 2014, 21:223-224.[葛芳芳, 李延峰, 孙宏博. Parkin相关的青少年型帕金森病一例[J]. 中国神经免疫学和神经病学杂志, 2014, 21:223-224.]
[2] Yamamura Y, Sobue I, Ando K, Iida M, Yanagi T. Paralysis agitans of early onset with marked diurnal fluctuation of symptoms[J]. Neurology, 1973, 23:239-244.
[3] Jiang YN, Chen NH. Advances in Parkinson's disease-causing gene Parkin[J]. Shen Jing Yao Li Xue Bao, 2015, 5:36-45.[姜懿纳, 陈乃宏. 帕金森病致病基因Parkin的研究进展[J]. 神经药理学报, 2015, 5:36-45.]
[4] West A, Periquet M, Lincoln S, Lücking CB, Nicholl D, Bonifati V, Rawal N, Gasser T, Lohmann E, Deleuze JF, Maraganore D, Levey A, Wood N, Dürr A, Hardy J, Brice A, Farrer M; French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility on Parkinson's Disease. Complex relationship between Parkin mutations and Parkinson disease[J]. Am J Med Genet, 2002, 114:584-591.
[5] da Costa CA, Sunyach C, Giaime E, West A, Corti O, Brice A, Safe S, Abou-Sleiman PM, Wood NW, Takahashi H, Goldberg MS, Shen J, Checler F. Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease[J]. Nat Cell Biol, 2009, 11:1370-1375.
[6] Biswas R, Bagchi A. A comprehensive computational study on pathogenic mis-sense mutations spanning the RING2 and REP domains of Parkin protein[J]. Gene, 2017, 610:49-58.
[7] Ambroziak W, Koziorowski D, Duszyc K, Górka-Skoczylas P, Potulska -Chromik A, S?awek J, Hoffman -Zacharska D. Genomic instability in the PARK2 locus is associated with Parkinson's disease[J]. J Appl Genet, 2015, 56:451-461.
[8] Simon-Sanchez J, Scholz S, Matarin Mdel M, Fung HC, Hernandez D, Gibbs JR, Britton A, Hardy J, Singleton A. Genomewide SNP assay reveals mutations underlying Parkinson disease[J]. Hum Mutat, 2008, 29:315-322.
[9] Asakawa S, Hattori N, Shimizu A, Shimizu Y, Minoshima S, Mizuno Y, Shimizu N. Analysis of eighteen deletion breakpoints in the parkin gene[J]. Biochem Biophys Res Commun, 2009, 389:181-186.
[10] Kitada T, Asakawa S, Matsumine H, Hattori N, Shimura H, Minoshima S, Shimizu N, Mizuno Y. Progress in the clinical and molecular genetics of familial parkinsonism[J]. Neurogenetics, 2000, 2:207-218.
[11] Schrag A, Schott JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism[J]. Lancet Neurol, 2006, 5:355-363.
[12] Jiang YN, Lou YX, Zhang Z, Chen NH. Some diseases caused by Parkin[J]. Zhongguo Yao Li Xue Tong Bao, 2016, 32:455-458.[姜懿纳, 娄钰霞, 张钊, 陈乃宏. Parkin相关疾病的研究进展[J]. 中国药理学通报, 2016, 32:455-458.]
[13] Hou HX, Zhang J, Wang X. Parkin gene and Parkinson's disease[J]. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi, 2008, 6:1190-1192.[侯焕喜, 张静, 王训. Parkin基因与帕金森病[J]. 中西医结合心脑血管病杂志, 2008, 6:1190-1192.]
[14] Hedrich K, Eskelson C, Wilmot B, Marder K, Harris J, Garrels J, Meija-Santana H, Vieregge P, Jacobs H, Bressman SB, Lang AE, Kann M, Abbruzzese G, Martinelli P, Schwinger E, Ozelius LJ, Pramstaller PP, Klein C, Kramer P. Distribution, type, and origin of Parkin mutations:review and case studies[J]. Mov Disord, 2004, 19:1146-1157.
[15] Li Q, Liu Y, Zhao Y, Zhu Y, Qiu ZJ. Screening of target genes for diagnosis and treatment of primary Parkinson's disease[J]. Shandong Yi Yao, 2017, 57:24-27.[李倩, 刘媛, 赵玉, 朱彧, 裘志军. 原发性帕金森病诊断、治疗的靶基因筛选[J]. 山东医药, 2017, 57:24-27.]
[16] Wei YH. Research progress on gene polymorphism of Parkinson's disease[J]. Shi Yong Lao Nian Yi Xue, 2019, 33:637-641.[魏颖鸿. 帕金森病基因多态性的研究进展[J]. 实用老年医学, 2019, 33:637-641.]
[17] Meles SK, Teune LK, De Jong BM, Dierckx RA, Leenders KL. Metabolic imaging in Parkinson disease[J]. J Nucl Med, 2017, 58:23-28.
[18] Song TB, Lu J. Research development of 18F-FDG and dopaminergic neuron function targeting PET brain imaging on evaluation of Parkinson disease[J]. Zhongguo Yi Xue Ying Xiang Ji Shu, 2019, 35:1884-1888.[宋天彬, 卢洁. 18F-FDG PET脑显像和多巴胺能神经元突触功能PET脑显像研究帕金森病进展[J]. 中国医学影像技术, 2019, 35:1884-1888.]
[19] Yi C, Shi XC, Xian WB, Luo GH, He Q, Tang GH, Chen L, Zhang XS. Application of 18F-DOPA PET imaging in the diagnosis and assessment of early -stage Parkinson's disease[J]. Zhonghua He Yi Xue Yu Fen Zi Ying Xiang Za Zhi, 2018, 38:731-735.[易畅, 史新冲, 冼文彪, 罗淦华, 何巧, 唐刚华, 陈玲,张祥松. 18F-DOPA脑PET显像对早期帕金森病的诊断及病情评估[J]. 中华核医学与分子影像杂志, 2018, 38:731-735.]
[20] Luo Y. Recommendations for treatment of primary Parkinson's disease[J]. Zhonghua Lao Nian Yi Xue Za Zhi, 1999, 18:133-134.[罗毅. 原发性帕金森病治疗的建议[J]. 中华老年医学杂志, 1999, 18:133-134.]
[21] Parkinson's Disease and Movement Disorders Group of Neurology Branch of Chinese Medical Association. Guidelines for the treatment of Parkinson's disease in China (Third Edition)[J]. Zhonghua Shen Jing Ke Za Zhi, 2014:428-433.[中华医学会神经病学分会帕金森病及运动障碍学组. 中国帕金森病治疗指南(第三版)[J]. 中华神经科杂志, 2014:428-433.]
[22] Zhang YH, Tang BS, Yan XX, Shen YW, Xu B. Clinical features of juvenile Parkinson's disease[J]. Lin Chuang Shen Jing Bing Xue Za Zhi, 2004, 17:8-10.[张玉虎, 唐北沙, 严新翔, 申亚巍, 许波. 青少年型帕金森病的临床特征[J]. 临床神经病学杂志, 2004, 17:8-10.]
[23] Winklhofer KF. The parkin protein as a therapeutic target in Parkinson's disease[J]. Expert Opin Ther Targets, 2007, 11:1543-1552.

选择文件类型/文献管理软件名称

选择包含的内容

2 常染色体隐性遗传性青少年型帕金森病临床特点及疗效评价

Clinical characteristics and therapeutic evaluation of autosomal recessive juvenil-onset Parkinson's disease

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	范咏言, 李晓欢, 马建军, 杨大伟, 梁可可, 石小雪. 帕金森病患者血清胆红素与睡眠障碍相关分析[J]. 中国现代神经疾病杂志, 2023, 23(8): 723-729.
[2]	任修德, 李涛, 范吉康, 王希森, 贾晓丹, 杨学军. 胶质母细胞瘤FGFR3-TACC3融合基因介导丙酮酸激酶M2入核促进DNA损伤修复基础研究[J]. 中国现代神经疾病杂志, 2023, 23(8): 745-757.
[3]	吴旭玲, 张安妮, 雷晓阳, 冯占辉, 王维, 贺电. 强直性肌营养不良症1型一例[J]. 中国现代神经疾病杂志, 2023, 23(8): 765-769.
[4]	侯玮佳, 于洋, 吴璠, 王玥, 朱志中, 巫嘉陵. 早期帕金森病患者起步异常定量分析[J]. 中国现代神经疾病杂志, 2023, 23(7): 627-632.
[5]	李跃文, 褚先舟, 李娟, 秦艳, 吴桐, 陈先文. BSCL2基因c.455A>G突变致远端型遗传性运动神经病V型一家系[J]. 中国现代神经疾病杂志, 2023, 23(7): 643-647.
[6]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[7]	邵暇荔, 张泳, 金莉蓉, 王剑. 震颤为主型帕金森病与特发性震颤患者脑灌注对比分析[J]. 中国现代神经疾病杂志, 2023, 23(6): 542-548.
[8]	王敏, 秦洁, 李岚昕, 李欣, 陈蕾. 2型糖尿病增加帕金森病风险相关机制研究进展[J]. 中国现代神经疾病杂志, 2023, 23(6): 566-570.
[9]	崔立立, 纪坤乾, 张正华, 张同霞, 赵玉英. 以排尿困难发病的SOD1基因变异致肌萎缩侧索硬化一例[J]. 中国现代神经疾病杂志, 2023, 23(5): 472-476.
[10]	姚莉萍, 王睿晗, 包翌, 蔡瀚林, 陈芹. 后部皮质萎缩临床及影像学特征分析[J]. 中国现代神经疾病杂志, 2023, 23(4): 326-334.
[11]	蔡洪钱, 张安妮, 徐子茜, 龚慧蓝, 曾红梅, 贺电. 伴PSEN2基因V214L突变的早发型阿尔茨海默病一家系临床研究[J]. 中国现代神经疾病杂志, 2023, 23(4): 335-340.
[12]	徐蓉, 宁泽淑, 康庆云, 陈波, 廖红梅, 杨理明, 吴丽文. 钾离子通道基因变异相关婴儿癫痫性脑病临床表型与基因变异特点分析[J]. 中国现代神经疾病杂志, 2023, 23(3): 196-204.
[13]	唐薇婷, 肖波. N-甲基-D-天冬氨酸受体GRIN2A基因变异与癫痫研究进展[J]. 中国现代神经疾病杂志, 2023, 23(2): 89-93.
[14]	李字林, 胡文瀚, 张凯. 癫痫外科常见病理类型体细胞突变研究进展[J]. 中国现代神经疾病杂志, 2023, 23(2): 115-123.
[15]	汤亚南. 儿童和青少年功能性神经系统疾病诊断与治疗进展[J]. 中国现代神经疾病杂志, 2023, 23(2): 143-147.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 常染色体隐性遗传性青少年型帕金森病临床特点及疗效评价

Clinical characteristics and therapeutic evaluation of autosomal recessive juvenil-onset Parkinson's disease

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价