酪氨酸羟化酶缺乏症所致多巴反应性肌张力不全5例患儿临床及基因研究  

Clinical and genetic study on 5 children with dopa - responsive dystonia due to tyrosine hydroxylase deficiency

作　　者：张尧[1] 李东晓[1] 刘怡[1] 金颖[1] 宋金青[1] 杨艳玲[1] Zhang Yao;Li Dongxiao;Liu Yi;Jin Ying;Song Jinqing;Yang Yanling(Department of Pediatrics ,Peking University First Hospital ,Beijing 100034, China)

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华实用儿科临床杂志》2018年第6期462-464,共3页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81471097）;国家重点研发计划（2017YFC1001704）;儿科遗传性疾病分子诊断与研究北京市重点实验室（BZ0317）

摘　　要：目的研究酪氨酸羟化酶（TH）缺乏症所致多巴反应性肌张力不全患儿的临床表现、基因突变及诊疗方法。方法选择2002年1月至2017年10月诊断并随访的5例TH缺乏症所致多巴反应性肌张力不全患儿（男童3例，女童2例），对患儿临床表现、实验室检查、治疗及TH相关TH基因突变进行分析。结果5例患儿来自不同家庭，于8个月～1岁8个月起病。5例均表现为肌张力不全和阵发性肌张力增高，智力正常或轻度落后，均曾被误诊为脑性瘫痪。2例有易疲劳和震颤，1例肢体松软伴抽搐发作。5例患儿TH基因存在不同类型的复合杂合突变，确诊为TH缺乏症所致多巴反应性肌张力不全。5例患儿TH基因共发现8种突变，6种已知突变，2种新突变[c.1077C〉A （p.C359X）和c.1228C〉T （p.R410C）]。经多巴丝肼治疗后[2.2～5.4 mg/（kg·d）]，3例智力运动恢复正常；2例显著好转，运动协调性稍差。结论TH缺乏症所致多巴反应性肌张力不全多于婴儿期起病，智力相对正常，以运动落后、肌张力不全为主要表现，常被误诊为脑性瘫痪，多巴丝肼治疗效果显著，病因诊断极为重要。ObjectiveTo explore the clinical characteristics, gene mutations, diagnosis and treatment of children with dopa-responsive dystonia due to tyrosine hydroxylase （TH） deficiency.MethodsFive patients （3 boys and 2 girls） with dopa-responsive dystonia due to TH deficiency were diagnosed and followed up from January 2002 to October 2017.The clinical manifestations, laboratory findings, treatment and TH gene mutations associated with TH deficiency were analyzed.ResultsFive patients came from different families.They had the onset at the age of 8 months to 20 months with dystonia, paroxysmal muscular hypertonia and normal intelligence or mild mental retardation.All of them had been misdiagnosed as cerebral palsy.Two cases with floppy limbs presented with fatigue and tremor.One case with floppy limbs presented with seizures.Complex heterozygous mutations were found in TH gene of all patients, which helped to confirm the diagnosis.Eight mutations were identified in TH gene.Six of them were reported.Two novel mutations, c.1077C〉A （p.C359X） and c. 1228C〉T （p.R410C） were detected.After the treatment by levodopa [2.2-5.4 mg/（kg·d）], significant improvement was observed.Three patients recovered their intellectual and motor activities.Two patients were dramatically improved but with slightly uncoordinated movements.ConclusionThe patients of dopa-responsive dystonia due to TH deficiency usually have the onset around one year of age with almost normal inte-lligence, motor retardation and dystonia.The patients are likely misdiagnosed as cerebral palsy.The treatment with levodopa can dramatically improve the symptoms.The etiological diagnosis is very important.

关 键 词：酪氨酸羟化酶缺乏症 肌张力不全 多巴反应性肌张力不全 多巴丝肼 

分 类 号：R746[医药卫生—神经病学与精神病学]