CAJ | 학술논문

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.
목적 총결다파반응성기장력장애(dopa-responsive dystonia,DRD)적림상특점,탐토기치료효과、수방결과급삼린산조감배화수해매Ⅰ (GCH Ⅰ)기인、락안산간화매(TH)기인돌변정황.방법 총결3개DRD가계공4례환자적림상자료,병대환자행GCH Ⅰ기인급TH기인검측.결과 4례환자균위녀성,기병년령위9 ～ 20(15.3±5.6)세,균이쌍하지강경、두동기병,수병정진전기중3례출현쌍수두동증상,1례환자출현전신뉴전,1례환자합병유사경,4례환자균유신경모중적표현.대4례환자진행소제량좌선다파치료,수방반년지10년불등,환자균유지속、명현적료효；차수시간연장소수제량감소,무장기복용좌선다파불량반응.대4례환자행GCH Ⅰ기인전장외현자돌변검측,1례환자정GCH Ⅰ기인잡합점돌변c.607G＞A(p.Gly203 Arg),1례환자위TH기인14호외현자복합잡합돌변(p.Y447Ter급p.V468M),여환자미견GCH Ⅰ기인급TH기인전장외현자점돌변.결론 장기수방발현소제량좌선다파대DRD환자구유현저이지구적료효,차무명현부작용.GCH Ⅰ기인급TH기인적검측가대DRD진행조기진단,대우인동기혹청소년기기병적기장력장애환자,무론유무가족사,균수행소제량다파알진단성치료.
Objective 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.