目的 报道1例首发症状为少年帕金森综合征的遗传性痉挛性截瘫11型(SPG11)患儿。方法 描述1例13岁发病的27岁男性患者的临床资料。结果 患者首发为抖动、肢体僵硬,逐渐出现运动迟缓、行走困难,服用左旋多巴类药物有效。MRI示胼胝体萎缩和侧脑室周围白质脱髓鞘改变;肌电图示神经传导速度正常。基因检测提示SPG11基因存在两处杂合突变：c.5867-1G>C和c.3687-2A>G。家系分析显示突变分别来自父方和母方,为复合杂合突变。结论 SPG11可以帕金森综合征为首发表现,少年起病的帕金森综合征患儿有必要进行全面基因筛查。
Objective To report a novel case of hereditary spastic paraparesis type 11 (SPG11) first presenting as juvenile Parkinsonism. Methods A 27 years old man first attack at 13 years old was reviewed. Results Parkinsonism-like features, such as tremor, rigidity, bradykinesia and gradually difficulty walking, were complained, and responded to dopaminergic therapy. MRI showed thin corpus callosum and hyper-intense T2WI lesions in periventricular regions. His nerve conduction velocity was normal. Genetic analysis detected two novel mutations, named c.5867-1G>C and c.3687-2A>G, in spastic paraplegia gene 11, which came from his father and mother separately. Conclusion Parkinsonism may be the inaugural presentation of SPG11, and a genetic test may be needed for the child with juvenile Parkinsonism.
[1] Salinas S, Proukakis C, Crosby A, et al.Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms[J]. Lancet Neurol, 2008, 7(12): 1127-1138.
[2] 林鹏飞,龚瑶琴,焉传祝. 遗传性痉挛性截瘫的分子遗传学研究进展[J]. 中华神经科杂志, 2015, 48(11): 1030-1038.
[3] Kang SY, Lee MH, Lee SK, et al.Levodopa-responsive parkinsonism in hereditary spastic paraplegia with thin corpus callosum[J]. Parkinsonism Relat Disord, 2004, 10(7): 425-427.
[4] Anheim M, Lagier-Tourenne C, Stevanin G, et al.SPG11 spastic paraplegia. A new cause of juvenile parkinsonism[J]. J Neurol, 2009, 256(1): 104-108.
[5] Paisan-Ruiz C, Guevara R, Federoff M, et al.Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations[J]. Mov Disord, 2010, 25(12): 1791-1800.
[6] Guidubaldi A, Piano C, Santorelli FM, et al.Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism[J]. Mov Disord, 2011, 26(3): 553-556.
[7] Ramirez-Zamora A, Gee L, Youn Y, et al.Pallidal deep brain stimulation for the treatment of levodopa-responsive juvenile dystonia and parkinsonism secondary to SPG11 mutation[J]. JAMA Neurol, 2017, 74(1): 127-128.
[8] Stevanin G, Santorelli FM, Azzedine H, et al.Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum[J]. Nat Genet, 2007, 39(3): 366-372.
[9] Stevanin G, Montagna G, Azzedine H, et al.Spastic paraplegia with thin corpus callosum: Description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity[J]. Neurogenetics, 2006, 7(3): 149-156.
[10] Hehr U, Bauer P, Winner B, et al.Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia[J]. Ann Neurol, 2007, 62(6): 656-665.
[11] Coutinho P, Barros J, Zemmouri R, et al.Clinical heterogeneity of autosomal recessive spastic paraplegias: Analysis of 106 patients in 46 families[J]. Arch Neurol, 1999, 56(8): 943-949.
[12] Simpson MA, Cross H, Proukakis C, et al.Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia[J]. Am J Hum Genet, 2003, 73(5): 1147-1156.
[13] Orlacchio A, Kawarai T, Totaro A, et al.Hereditary spastic paraplegia: clinical genetic study of 15 families[J]. Arch Neurol, 2004, 61(6): 849-855.
[14] Okubo S, Ueda M, Kamiya T, et al.Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum[J]. Acta Neurol Scand, 2000, 102(3): 196-199.
[15] Davison C.Pallido-pyramidal disease[J]. J Neuropathol Exp Neurol, 1954, 13(1): 50-59.
[16] Tranchant C, Koob M, Anheim M.Parkinsonian-pyramidal syndromes: a systematic review[J]. Parkinsonism Relat Disord, 2017, 39: 4-16.
[17] Park JS, Blair NF, Sue CM.The role of ATP13A2 in Parkinson's disease: clinical phenotypes and molecular mechanisms[J]. Mov Disord, 2015, 30(6): 770-779.
[18] Yoshino H, Tomiyama H, Tachibana N, et al.Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism[J]. Neurology, 2010, 75(15): 1356-1361.
[19] Di Fonzo A, Dekker MC, Montagna P, et al.FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome[J]. Neurology, 2009, 72(3): 240-245.
[20] Wijemanne S, Jankovic J.Dopa-responsive dystonia–clinical and genetic heterogeneity[J]. Nat Rev Neurol, 2015, 11(7): 414-424.
[21] Bandmann O, Weiss KH, Kaler SG.Wilson's disease and other neurological copper disorders[J]. Lancet Neurol, 2015, 14(1): 103-113.
[22] Machado A, Chien HF, Deguti MM, et al.Neurological manifestations in Wilson's disease: Report of 119 cases[J]. Mov Disord, 2006, 21(12): 2192-2196.
[23] 中华医学会神经病学分会帕金森病及运动障碍学组,中国医师协会神经内科医师分会帕金森病及运动障碍专业委员会. 脑组织铁沉积神经变性病诊治专家共识[J]. 中华医学杂志, 2016, 96(27): 2126-2133.
[24] Schneider SA, Hardy J, Bhatia KP.Syndromes of neurodegeneration with brain iron accumulation (NBIA): an update on clinical presentations, histological and genetic underpinnings, and treatment considerations[J]. Mov Disord, 2012, 27(1): 42-53.
[25] Thomas M, Hayflick SJ, Jankovic J.Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration[J]. Mov Disord, 2004, 19(1): 36-42.
