摘要目的 总结多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)的临床特点,探讨其治疗效果、随访结果及三磷酸鸟苷环化水解酶Ⅰ (GCH Ⅰ)基因、酪氨酸羟化酶(TH)基因突变情况.方法 总结3个DRD家系共4例患者的临床资料,并对患者行GCH Ⅰ基因及TH基因检测.结果 4例患者均为女性,起病年龄为9 ～ 20(15.3±5.6)岁,均以双下肢僵硬、抖动起病,随病程进展其中3例出现双手抖动症状,1例患者出现全身扭转,1例患者合并有斜颈,4例患者均有晨轻暮重的表现.对4例患者进行小剂量左旋多巴治疗,随访半年至10年不等,患者均有持续、明显的疗效；且随时间延长所需剂量减少,无长期服用左旋多巴不良反应.对4例患者行GCH Ⅰ基因全长外显子突变检测,1例患者呈GCH Ⅰ基因杂合点突变c.607G＞A(p.Gly203 Arg),1例患者为TH基因14号外显子复合杂合突变(p.Y447Ter及p.V468M),余患者未见GCH Ⅰ基因及TH基因全长外显子点突变.结论 长期随访发现小剂量左旋多巴对DRD患者具有显著而持久的疗效,且无明显副作用.GCH Ⅰ基因及TH基因的检测可对DRD进行早期诊断,对于儿童期或青少年期起病的肌张力障碍患者,无论有无家族史,均需行小剂量多巴胺诊断性治疗.

abstractsObjective To investigate the clinical characteristics,treatment effect,long-term follow up results,guanosine triphosphate (GTP) cyrclohydrolase Ⅰ (GCH Ⅰ)gene and tyrosine hydroxylase(TH) gene mutations in patients with dopa-responsive dystonia (DRD).Methods The clinical features of 3 families with 4 affected members were analyzed and all of 4 patients were screened for mutations of the GCH Ⅰ gene and TH gene with DNA sequences.Results Four patients were females,average age at onset was (15.3 ± 5.6) years (range:from 9 to 20 years).The initial symptoms were a gait disorder,stiffness or tremor of the lower limbs in all patients presented with diurnal fluctuation.As the increase of disease duration,bilateral hand tremor was found in three patients,systemic torsion was found in one patient and torticollis was found in one patient.All patients' symptoms were in complete remission after administration of low dose of levodopa.Four patients were followed up for 0.5 to 10.0 years,and all were still responsive to the levodopa treatment and effective dosage was decreased as the increase of the disease duration.No longterm side effects of levodopa had occurred after long-term treatment.One patient was found to have c.607G ＞A(p,Gly203Arg) heterogenetic mutation in GCH I gene.Molecular analysis revealed a compound heterozygous mutation in the TH gene (p.Y447Ter and p.V468M) in one patient.No point mutations in both genes were found in other patients.Conclusions DRD patients have dramatic and sustained response to levodopa and no long-term side effects of levodopa after long-term treatment.The detection of GCH Ⅰ and TH gene mutations is helpful in early diagnosis but the negative results could not exclude the diagnosis of DRD.