Abstract: Objective　To analyze the clinical and genetic mutation characteristics of children with Dopa-responsive dystonia（DRD）. Methods　The clinical manifestations，laboratory tests and treatment effects of DRD in 6 patients admitted to neurology clinic from August 2016 to March 2019 were retrospectively analyzed. Results　Of the 6 patients with DRD，two were male and four were female. The age ranged from 13 months to 11 years and 5 months. The initial symptom was lower limb dysmobility，and the disease was progressing. The main symptoms on visiting doctors were foot varus（3 cases），abnormal posture（4 cases），involuntary movement（3 cases），spastic torticollis（1 case），epileptic seizures（1 case），and mental and growth retardation（1 case）. Five patients were with diurnal fluctuation. Six patients received gene detection，and five patients had mutations in GCH1 gene［4 were novel mutations，c.131C＞G（p.Ala44Gly），c.325T＞C（p.Tyr109His），c.225C＞G（p.Tyr75*）and c.5dupA（p.Lys3Glufs*62）］. One patient had  heterozygous mutations in TH gene，c.698G＞A（p.Arg233His）and c.971_982dup，and the latter was a novel mutation. Six patients were treated with Madopar，and significant improvement was observed in five cases. Three patients showed excitement and  lower limbs jitter during the treatment，and the symptoms disappeared after adjusting the drug dose in two patients. Conclusion　The majority of DRD manifests as limb dysfunction and/or gait abnormality with diurnal fluctuation，and there is no exact correlation between genotype and phenotype. The newly discovered four GCH1 mutations and one TH mutation have enriched the gene mutation profile of DRD.

Key words: dystonia, mutation, levodopa, diurnal fluctuation

摘要： 目的　分析多巴反应性肌张力障碍（DRD）患儿临床及基因突变特点。方法　收集2016年8月至2019年3月于上海交通大学医学院附属上海儿童医学中心神经内科就诊的6例DRD患儿临床表现、实验室检查及治疗效果进行回顾性分析。结果　6例患儿中男2例，女4例，就诊年龄1岁1月龄至11岁5月龄。首发症状多为下肢活动障碍，病情呈进行性进展，就诊时主要症状存在足内翻（3例）、姿势异常（4例）、不自主运动（3例）、痉挛性斜颈（1例）、癫痫样发作（1例）、智力及生长发育落后（1例）；5例具有晨轻暮重特点。6例均行基因检测，5例检测到GCH1基因突变［4例为新发突变，分别为c.131C＞G（p.Ala44Gly）、c.325T＞C（p.Tyr109His）、c.225C＞G（p.Tyr75*）与c.5dupA（p.Lys3Glufs*62）］，1例为TH基因c.698G＞A（p.Arg233His）和c.971_982dup的复合杂合突变，其中c.971_982dup为新发突变。6例均给予美多芭治疗，除1例效果不明显外，其余5例症状均明显好转。3例患儿治疗中出现兴奋、双下肢抖动表现，2例调整药物剂量后症状消失。结论　绝大多数DRD表现为晨轻暮重的肢体活动障碍和（或）步态异常，其临床表型与基因型之间尚无确切对应关系。新发现的4个GCH1突变和1个TH突变丰富了DRD基因突变谱。

关键词: 肌张力障碍, 突变, 左旋多巴, 晨轻暮重