多巴反应性肌张力障碍一家系四氢生物蝶呤代谢与基因研究

Study on tetrahydrobiopterin metabolism and gene mutation for dopa-responsive dystonia-a family report.

目的 探讨多巴反应性肌张力障碍 (DRD)其四氢生物蝶呤 (BH4)代谢及基因突变与临床表型关系。方法 对DRD的一家系 4人进行苯丙氨酸 (Phe)和BH4负荷试验、尿蝶呤谱分析 ,对所有成员进行三磷酸鸟苷环化水解酶 1基因 (GCH1)检测。结果 3例DRD患儿及母亲平均血Phe浓度、Phe与酪氨酸比值 (Phe/Tyr)在Phe负荷试验 3～ 4h明显高于正常对照组 ,负荷 2h尿生物蝶呤水平上升低于对照组 ;3例患儿服用BH4后上述结果恢复正常。除父亲未检测到基因突变外 ,所有成员GCH1突变类型为IVS5 +3insT。 2例有症状者小剂量左旋多巴 (5 0～ 6 0mg/d)治疗有效。结论 DRD者BH4代谢有不同程度异常 ,临床表型差异较大 ,对原因不明的肌张力障碍者可做DRD的筛查。

Objective To evaluate the tetrahydrobiopterin(BH 4) metabolism,gene mutation and clinical manifestation in patients with dopa responsive dystonia(DRD).Methods Four members of a DRD family were performed phenylalanine(Phe) and BH 4 loading test as well as urinary pterin analysis.Mutation analysis of GTP cyclohydrolase 1 gene(GCH1) was done in all family members.Results The levels of Phe and phenylalanine /tyrosine(Phe/Tyr) were higher in three patients and their mothers than that in control at 3～4h after Phe loading test.The increase of urinary biopterin levels at 2h after Phe loading was lower in patients and their mothers than that in control.The inrease could reverse to normal after BH 4 administration in three patients.The IVS5+3insT mutation was found in all family members except fathers.Conclusion There is abnormality of BH 4 metabolism with different degrees and there are various clinical phenotypes in patients with DRD.The screening for DRD can be carried out in all patients with dystonia of unknown causes.