多巴反应性肌张力障碍临床分析及GCH Ⅰ基因突变的研究

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(GCH Ⅰ)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GCH Ⅰ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GCH Ⅰ基因突变检测,在3例患儿中发现了2种GCH Ⅰ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.GCH Ⅰ基因突变类型与临床表型之间有一定关联,对GCH Ⅰ基因突变的检测有助于不典型病例的早期诊断.

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

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 levodopa for 3 months and no long-term side effects of levodopa had occurred. Two independent mutations were found in three patients. Gln161Pro, 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 levodopa. There may be a correlation between genotype and phenotype. The detection of GCH I mutations is helpful in early diagnosis of non-typical cases.