多巴反应性肌张力障碍临床分析及GCHⅠ基因突变的研究  

Clinical analysis of dopa-responsive dystonia and mutation analysis of the GCH Ⅰ gene

作　　者：谢卉[1] 吴志英[1] 王柠[1] 李智文[1] 林珉婷 慕容慎行[1] 

机构地区：[1]福建医科大学附属第一医院神经内科,福州350005 [2]福建省神经病学研究所

出　　处：《中华儿科杂志》2006年第7期492-495,共4页Chinese Journal of Pediatrics

基　　金：福建省重大科技项目(2002Y001);福建省卫生厅青年基金项目(2005-2-1);福建医科大学青年教师科研基金项目(FJGXQ04002)

摘　　要：目的探讨多巴反应性肌张力障碍(DRD)临床及GTP环化水解酶Ⅰ(GCHⅠ)基因突变特点。方法对14例DRD患儿的临床资料进行总结分析,并对其中6例进行了GCHⅠ基因全长外显子的突变检测。结果14例患儿平均发病年龄为(10±3)岁,女性起病较男性早,发病年龄(9±4)岁,男性发病年龄(12±1)岁。常见的首发症状为步态异常、下肢僵硬和震颤。伴晨轻暮重者9例(64％)。小剂量多巴制剂治疗3个月后痊愈13例(93％),显效1例(7％),长期随访未发现多巴制剂的不良反应。对6例患儿进行GCHⅠ基因突变检测,在3例患儿中发现了2种GCHⅠ基因突变。其中一家系2例患儿存在第6号外显子的Lys224Arg杂合错义突变,临床表型较轻,与国外研究报道一致。在1例散发病例中发现了国际上未曾报道过的位于第3号外显子的Gln161Pro突变,临床表型较重。结论DRD临床表现复杂多样,晨轻暮重是其特点之一。多巴制剂对其有快速、显著和持续的疗效。GCHⅠ基因突变类型与临床表型之间有一定关联,对GCHⅠ基因突变的检测有助于不典型病例的早期诊断。Objective To investigate the clinical characteristics and GCH I gene mutations in patients with dopa-responsive dystonia （DRD）. Methods The clinical features of 3 families with 6 affected members and 8 sporadic cases were analyzed to determine the clinical characteristics, and 2 families with 4 affected members and 2 sporadic cases were screened for mutations of the GCH I gene. Results Age at onset was （ 10 ± 3 ） years. Onset occurred earlier in female （9 ± 4） years than in male （ 12 ± 1 ） years. The initial symptom was a gait disorder, dystonia or tremor in most patients and nine patients （64%） presented with diurnal fluctuation. Thirteen patients （93%） were cured and one was improved after administration of low doses of levedopa for 3 months and no long-term side effects of levodopa had occurred. Two independent mutations were found in three patients. Glnl61Pro, a new missense mutation, was found in a sporadic case, leading to a relatively severe phenotype. The two patients with mild phenotype in one family were found to have Lys224Arg mutation, as previously described. Conclusions DRD patients have diverse phenotypes and diurnal fluctuation is an important feature. They have dramatic and sustained response to levedopo. There may be a correlation between genotype and phenotype. The detection of GCH Ⅰ mutations is helpful in early diagnosis of non-typical cases.

关 键 词：张力失调 GTP环化水解酶 突变 

分 类 号：R741[医药卫生—神经病学与精神病学]