多巴反应性肌张力障碍

目的：探讨多巴反应性肌张力障碍的临床特点、诊断和治疗方法。方法：回顾性分析10例多巴反应性肌张力障碍患的临床表现、诊断方法和治疗效果。结果：多巴反应性肌张力障碍发病年龄较早,多见于女孩,表现为肌张力障碍或合并帕金森综合征,呈昼间波动,应用左旋多巴治疗有明显疗效。结论：对幼年起病的肌张力障碍或帕金森综合征患,应首先使用左旋多巴治疗,以筛选出多巴反应性肌张力障碍,使患能够保持正常生活质量。     

多巴反应性肌张力障碍临床分析

目的回顾性分析多巴反应性肌张力障碍患者的临床特点和治疗原则。方法选择2005年3月-2010年7月门诊或住院治疗且诊断明确的多巴反应性肌张力障碍患者,面对面采集临床资料并门诊或电话随访,对其性别、年龄、发病年龄、家族史、首发症状、就诊症状、诊断延误时间及治疗过程进行分析。结果共21例患者人组,男4例、女17例,平均发病年龄（7．19±3．40）岁,平均诊断延误时间（13．76±11.38）年。均以肢体肌张力障碍为首发症状,20例（95．24％）呈现晨轻暮重现象,6例（28．57％）伴帕金森样症状,2例（9．52％）伴痉挛性截瘫;经小剂量左旋多巴,多巴丝肼治疗后症状显著缓解。随访18例患者,仅1例治疗后仍遗留肢体残疾;3例失访。随访期间左旋多巴／多巴丝肼平均维持剂量（175．35±113．51）mg／d,3例患者辅助应用盐酸苯海索（4.6mg／d）治疗。结论多巴反应性肌张力障碍患者多于儿童期以肢体肌张力障碍发病,小剂量左旋多巴／多巴丝肼治疗效果显著。因此,对于儿童肌张力障碍或青年帕金森样症状患者应行小剂量左旋多巴,多巴丝肼诊断性治疗,以降低多巴反应性肌张力障碍的误诊率。     

多巴反应性肌张力障碍临床分析

目的回顾性分析多巴反应性肌张力障碍患者的临床特点和治疗原则。方法选择2005年3月-2010年7月门诊或住院治疗且诊断明确的多巴反应性肌张力障碍患者,面对面采集临床资料并门诊或电话随访,对其性别、年龄、发病年龄、家族史、首发症状、就诊症状、诊断延误时间及治疗过程进行分析。结果共21例患者入组,男4例、女17例,平均发病年龄(7.19±3.40)岁,平均诊断延误时间(13.76±11.38)年。均以肢体肌张力障碍为首发症状,20例(95.24%)呈现晨轻暮重现象,6例(28.57%)伴帕金森样症状,2例(9.52%)伴痉挛性截瘫;经小剂量左旋多巴/多巴丝肼治疗后症状显著缓解。随访l 8例患者,仅1例治疗后仍遗留肢体残疾;3例失访。随访期间左旋多巴/多巴丝肼平均维持剂量(175.35±113.51)mg/d,3例患者辅助应用盐酸苯海索(4～6 mg/d)治疗。结论多巴反应性肌张力障碍患者多于儿童期以肢体肌张力障碍发病,小剂量左旋多巴/多巴丝肼治疗效果显著。因此,对于儿童肌张力障碍或青年帕金森样症状患者应行小剂量左旋多巴/多巴丝肼诊断性治疗,以降低多巴反应性肌张力障碍的误诊率。     

GCH1基因新的移码突变引起的多巴反应性肌张力障碍1例报告和简要回顾

正多巴反应性肌张力障碍(Dopa-responsive dystonia,DRD)~([1])是1976年由Masaya Segawa首次报道,又称Segawa病,其临床特征包括肌张力障碍、步态障碍、僵硬、轻度帕金森病、日间波动和对左旋多巴的剧烈反应等。患者通常对左旋多巴反应良好,症状明显改善,甚至消失。多巴反应性肌张力障碍(DRD)是一种可治疗的遗传性疾病,因此识别它是非常重要的。本研究拟通过报道1例DRD GCH1基因新的移码突变,以提高临床对DRD诊断及预后的认识,以免误诊。     

一个遗传性多巴反应性肌张力障碍家系的临床特点及GCH-Ⅰ基因突变分析

目的 探讨一遗传性多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)家系临床特点和相关基因突变.方法 收集一个多巴反应性肌张力障碍家系全部家庭成员临床资料并随访,采集家系成员静脉血,常规提取基因组DNA,利用PCR技术扩增三磷酸鸟苷环化水解酶Ⅰ(guanosine triphosphate cyclohydrolase 1,GCH-Ⅰ)基因全部6个外显子,进行DNA直接测序并分析.结果 该家系患病成员临床主要表现为肌张力障碍和帕金森综合征,但症状严重程度个体差异大,所以患者对多巴丝肼治疗均有较好反应,1例患者长期大剂量不规律使用左旋多巴后出现异动症.基因测序显示4例患病成员GCH-Ⅰ第四外显子102号碱基由胸腺嘧啶替换为腺嘌呤(T →A),并导致176位丝氨酸(Ser)转变为精氨酸(Arg) Arg176 Ser,该突变类型尚未见文献报道.其余家系成员未发现GCH-Ⅰ基因突变.结论 多巴反应性肌张力障碍临床表现在同一家系不同个体之间可有较大差异,部分患者长期大量不规律使用左旋多巴亦可导致异动症产生.GCH-Ⅰ基因第四外显子102号碱基 (T →A)突变是DRD患病的分子遗传学原因之一.     

多巴反应性肌张力障碍的临床特点

目的研究多巴反应性肌张力障碍患者的临床特点。方法对16例家族性患者和10例散发性多巴反应性肌张力障碍患者进行病史采集、神经系统体格检查和CT或MRI检查,所得数据应用SPSS13.0软件进行统计分析。结果26例患者,男10例,女16例;发病年龄为4～48岁,平均(17.46±12.95)岁。(1)首发症状:儿童期(12例)和青春期(6例)发病患者多以肌张力障碍为首发症状,成年期(8例)发病者则以帕金森综合征或肌张力障碍发病。(2)症状波动性:儿童期组和青春期组患者症状均呈现日间波动性,成年期组仅4例症状具有日间波动性,3组相比差异具有显著性意义(χ2=10.227,P=0.006);而且症状波动性与年龄呈负相关(r=#0.715,P<0.01)。(3)姿势性震颤:3组患者姿势性震颤的发生率差异具有显著性意义(χ2=8.073,P=0.018),其中以儿童期发病者发生率最低(5/12),成年期发生率最高(8/8);姿势性震颤的发生与患者年龄呈正相关(r=0.483,P=0.012)。(4)腱反射:3组间腱反射亢进发生率差异无显著性意义(χ2=5.303,P=0.071),腱反射亢进发生率与年龄呈负相关(r=#0.356,P=0.044)。(5)药物反应:26例患者均对左旋多巴治疗有明显而持续的反应。结论多巴反应性肌张力障碍临床表现呈多样化,临床表现与年龄密切相关。左旋多巴对多巴反应性肌张力障碍患者可产生明显而持续的疗效。     

多巴反应性肌张力障碍临床分析及文献复习

目的 探讨多巴反应性肌张力障碍(DRD)患者的临床特点.方法 对2例DRD患者的临床资料进行详细分析.结果 2例患者均为成人起病的DRD,具备DRD的特征性临床表现.结论 DRD有特征性的临床表现及特殊治疗方法,如能早期诊断,早期使用小剂量左旋多巴制剂治疗且维持用药则预后良好.     

酪氨酸羟化酶基因新型突变所致多巴反应性肌张力障碍1例

多巴反应性肌张力障碍临床罕见，发病率低。本文报告1例酪氨酸羟化酶（tyrosine hydroxylase, TH基因新型突变致多巴反应性肌张力障碍患者的临床资料，为临床诊治提供参考。患者为29岁女性，肢体震颤伴手足姿势异常19年，儿童期急性起病，慢性加重，主要表现为四肢震颤，行走时足尖着地及双手肌肉痉挛，症状存在昼夜波动性特点。查体可见双上肢轻微姿势性及静止性震颤。基因检测提示患者TH基因EXON9 C.943G>A错义突变（遗传自父亲）及TH基因EXON8 C.851A>G错义突变（遗传自母亲）的杂合突变，C.851A>G位点既往未见报告。予小剂量左旋多巴治疗，患者症状明显改善。分析该病例特点及文献回顾表明，多巴反应性肌张力障碍患者诊断主要依赖于基因检测，且不同的临床表型对左旋多巴反应不同。     

多巴反应性肌张力障碍32例临床分析

目的 探讨多巴反应性肌张力障碍(dopa-responsive dystonia, DRD)的临床特点.方法 对32例DRD患者从发病年龄,临床症状与体征及其治疗等方面进行回顾性分析.结果 32例患者,男10例,女22例,发病年龄为2-37岁.未成年发病多以肌张力障碍为首发症状,成年期发病多以帕金森综合征起病.未成年发病患者表现日间症状波动性大且腱反射亢进的发生率较高,而成年期发病患者姿势性震颤发生率较高.未成年发病患者中有家族史者占50%,而在成年期起病患者有家族史者占75%.以性别分组后,男性多以肌张力障碍起病,女性这一表现并不明显.对32例患者进行小剂量左旋多巴治疗,有持续明显的疗效.结论 DRD患者具有临床表现多样化的特点,临床表现与年龄密切相关.小剂量左旋多巴对DRD患者具有显著而持久的疗效.     

早发性肌张力障碍-帕金森综合征1例并文献复习

目的探讨早发性肌张力障碍-帕金森综合征的临床表现和治疗方法。方法报道1例早发性肌张力障碍-帕金森综合征患者的临床资料,结合复习国内外文献对早发性肌张力障碍-帕金森综合征的临床表现及治疗方法进行回顾性分析。结果早发性肌张力障碍-帕金森综合征是一种肌张力障碍叠加综合征,在肌张力障碍的同时伴有帕金森病症状,丘脑底核-脑深部电刺激治疗能够部分缓解患者的症状。结论早发性肌张力障碍-帕金森综合征可选择丘脑底核-脑深部电刺激进行治疗。     

Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene

OBJECTIVE—Hereditary progressive dystonia withpronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD))is a childhood onset dystonia which responds to levodopa. Variousclinical signs and symptoms of HPD/DRD have been recognised to date.Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recentlyidentified as the cause of HPD/DRD. In the present study, the GTP-CH-Igene and the clinical features of eight HPD/DRD patients from sixfamilies were analysed to determine the correlationsbetween clinical expression and the mutations in the GTP-CH-I gene.
METHODS—The exons, exon-intron junctions, and anindispensable part of the 5' flanking region of the GTP-CH-I gene weresequenced in the eight clinically diagnosed patients with HPD/DRD andtheir asymptomatic parents.
RESULTS—Three independent mutations in theGTP-CH-I gene were found in three patients. One of the patients and herasymptomatic mother were heterozygous for a novel mutation at theinitiation codon. The three patients with dissimilar GTP-CH-I mutationsexhibited similar clinical features. The other five patients withnormal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents.
CONCLUSIONS—A novel initiation codon mutation wasfound in a Japanese patient with HPD/DRD. The clinical manifestationscommon to the patients with HPD/DRD with a mutated GTP-CH-I gene werealso identified. Although focal manifestations of HPD/DRD associatedwith the mutations of this gene will be broadened, it is inferred thatthese clinical features are fundamental to HPD/DRD caused by mutationsin this gene.

     

Positron emission tomographic studies of dopa-responsive dystonia and early-onset idiopathic parkinsonism

There are two major syndromes presenting in the early decades of life with dystonia and parkinsonism: dopa-responsive dystonia (DRD) and early-onset idiopathic parkinsonism (EOIP). DRD presents predominantly in childhood with prominent dystonia and lesser degrees of parkinsonism. EOIP presents before age 40 with parkinsonism (often with associated dystonia). Both disorders are exquisitely sensitive to levodopa, although the long-term prognosis in each appears to be different. Some have suggested, however, that DRD is a form of EOIP. We performed positron emission tomography with 6-fluorodopa in 10 patients with DRD and 18 patients with EOIP to study the integrity of their nigrostriatal dopaminergic systems. In DRD, we found normal striatal FD uptake. In contrast, patients with EOIP had reduced striatal FD uptake. We conclude that the pathophysiologies of DRD and EOIP are distinct. Although both disorders presumably represent a deficiency of striatal dopamine, the results suggest that in DRD dopa uptake, decarboxylation, and storage mechanisms are intact. This may explain the sustained response of DRD to low doses of levodopa. 6-Fluorodopa positron emission tomography distinguishes DRD from EOIP.     

Clinical Spectrum of Dopa-Responsive Dystonia and Related Disorders

Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study.     

Successful treatment of childhood onset symptomatic dystonia with levodopa.

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms.     

Phenocopies in a large GCH1 mutation positive family with dopa responsive dystonia: confusing the picture?

BACKGROUND: Dopa responsive dystonia (DRD) is a disorder characterised by childhood onset dystonia but a wide range of clinical presentations has now been described. OBJECTIVE: To study a large Canadian family with presumed DRD. METHODS: The clinical features of the family were collected before molecular genetic mutational analysis. RESULTS: All nine individuals in whom a clinical diagnosis of DRD was definite or probable were heterozygous for a GCH1 gene deletion. However, eight of nine possibly clinically affected members did not carry the GCH1 mutation. CONCLUSIONS: Great care must be taken in diagnosing DRD even in families with the classic phenotype, because of potential phenocopies of the disease.     

Four novel mutations in the GCH1 gene of Chinese patients with dopa‐responsive dystonia

Mutation detection in the guanosine triphosphate cyclohydrolase I gene (GCH1) was performed from 4 female patients with dopa‐responsive dystonia (DRD). DNA sequencing revealed the presence of four novel mutations including c.2T>C(M1T), c.239G>A(S80N), c.245T>C(L82P), and IVS5+3 del AAGT. These four mutations were not found in 100 genetically unrelated healthy controls with the same ethnic background band. In all 3 childhood‐onset patients, DRD started in the legs, and missense mutations were located in the coding region of GCH1. Deletion mutation in the fifth exon–intron boundary of GCH1 was detected in the adult‐onset patient. Although the data presented here do not provide sufficient evidence to establish a genotype–phenotype correlation of DRD, it is important to know the clinic features and genetic defects of DRD patients, which will help prenatal diagnosis, early diagnosis, evaluate the prognosis, and facilitate causal therapy with levodopa. © 2010 Movement Disorder Society     

多巴反应性肌张力障碍15例临床分析

目的 探讨多巴反应性肌张力障碍(DRD)的病因、临床特点及治疗，加强对该病的认识。方法对15例DRD患者的临床资料进行回顾性分析。结果平均发病年龄11．5岁，平均病程8．9年，均为慢性起病，首发症状多从下肢肌张力障碍开始，症状有明显的昼间波动，有晨轻暮重现象。小剂量多巴制剂有显著而持久的疗效。结论本病是一种较为罕见的遗传性运动障碍性疾病，小剂量多巴制剂疗效显著；对儿童期起病的肌张力障碍性患者，应考虑DRD的可能性，早期诊治，预后良好。