摘要目的 总结经基因诊断确诊的特殊多巴反应性肌张力障碍(dopa responsive dystonia,DRD)患者的临床特点,结合文献探讨DRD患者左旋多巴药物治疗有效性及女性患者孕期用药安全性.方法 分析2例DRD患者症状、治疗药物及疗效,检测患者三磷酸鸟苷环化水解酶Ⅰ(GCH1)基因与酪氨酸羟化酶(TH)基因.结果 病例1为青年男性患者,临床主要表现为书写痉挛及下肢僵硬,症状有晨轻暮重,但是小剂量多巴丝肼不能完全控制书写痉挛症状,多巴丝肼加量后,书写痉挛症状仍偶有发作.病例2为青年女性患者,主要临床表现为步态异常,服用左旋多巴及安坦可完全控制症状.该患者在孕期自行服用左旋多巴及安坦,孕38周时产一健康女婴.直接测序检测患者的GCH1与TH基因全长外显子,病例1患者携带GCH1基因突变c.230C＞ G(p.S77C),该突变为新的致病性突变.病例2患者携带GCH1基因c.628delC(p.His210Thrfs*5)突变,该突变在前期研究已被报道.2例患者均未检测出TH基因突变.结论 大多数DRD患者对左旋多巴疗效良好,但书写痉挛症状对左旋多巴反应欠佳.前期文献回顾均提示DRD患者孕期使用左旋多巴单药治疗无不良事件发生.

abstractsObjective To investigate the efficiency of levodopa in dopa responsive dystonia (DRD) patients and drugs safety in pregnancy cases confirmed by genetic detection.Methods The clinical characteristics of two patients were analyzed.Direct sequences were performed in guanosine triphosphate (GTP) cyclohydrolase Ⅰ (GCH1) gene and tyrosine hydroxylase (TH) gene mutation screening.Results Case 1 was a young man exhibiting writer's cramp and dystonia of lower legs with marked diurnal fluctuation.Writer's cramp could not be relieved by treatment of low dose levodopa/benserazide.After increasing dose,the symptom of writer's cramp appeared occasionally.Case 2 was a young woman who experienced gait disorder.The symptom disappeared completely by levodopa treatment.She used levodopa and benzhexol during pregnancy.By 38 gestational weeks,she gave birth to a healthy baby.Sequence analysis of GCH1 gene in case 1 revealed a mutation (c.230C ＞ G p.S77C) that is a novel pathogenic mutation.The confirmed mutation c.628delC (p.His210Thrfs* 5) found in case 2 had been reported previously.No mutations in TH gene were detected in two patients.Condnsions Most of DRD patients have dramatic response to levodopa,but patients exhibited writer' s cramp may respond to levodopa incompletely.The previous reports indicate that no adverse events have been reported in DRD pregnant women with the monotherapy of levodopa.