TH基因变异致婴儿多巴反应性肌张力障碍4例临床和基因分析

目的探讨婴儿起病的多巴反应性肌张力障碍(DRD)的临床及遗传特征。方法回顾分析2016年4月—2020年6月收治的4例婴儿期起病的DRD患儿的临床资料。结果4例患儿中,男性3例、女性1例,起病年龄2~7个月。临床表现为发育落后或发育倒退,肌无力,肌张力障碍。患儿血生化、血氨、血乳酸无异常;脑电图、头颅磁共振成像(MRI)均无明显异常。患儿常规染色体检查无异常,发现TH基因复合杂合致病性变异。例1变异位点c.457C>T遗传自父亲,c.1196C>T遗传自母亲;例2 c.698G>A遗传自父亲,c.1293+5G>C遗传自母亲;例3 c.880G>C遗传自父亲,c.690C>A遗传自母亲;例4 c.739G>A遗传自父亲,c.1293+5G>C遗传自母亲;均为已报道的致病性变异。例1、2、3患儿确诊后予小剂量多巴丝肼治疗,逐渐加量至获得最佳疗效;随访至今1.5~3年,目前服药最大剂量达20~25 mg/(kg·d),均基本恢复;例4现多巴丝肼用量12 mg/(kg·d),激动时仍有肌张力障碍表现,继续缓慢加量中。结论婴儿起病的DRD早期症状无特殊性,应尽早行遗传学检测,多巴丝肼治疗效果好。

Clinical and genetic analysis of dopa-responsive dystonia caused by compound heterozygous mutation of TH gene in 4 infants

Objective To explore the clinical and genetic characteristics of dopa-responsive dystonia(DRD)in infants.Methods The clinical data of DRD in 4 infants admitted from April 2016 to June 2020 were retrospectively analyzed.Results In the 4 children(3 boys and 1 girl)the onset age ranged from 2 months to 7 months.The clinical manifestations were developmental retardation or regression,muscle weakness and dystonia.There were no abnormalities in blood biochemistry,blood ammonia and blood lactic acid tests.Electroencephalogram and cranial magnetic resonance imaging(MRI)showed no obvious abnormality.There was no abnormality in routine chromosomal examination,while the compound heterozygous pathogenic variation of TH gene was found.In case 1,c.457 C>T was inherited from the father and c.1196C>T was inherited from the mother.In case 2,c.698G>A was inherited from the father and c.1293+5G>C was inherited from the mother.In case 3,c.880 G>C was inherited from father and c.690 C>A was inherited from the mother.In case 4,c.739 G>A was inherited from the father and c.1293+5 G>C was inherited from the mother.All of them were reported to be pathogenic variants.Cases 1,2,and 3 were treated with low dose of dopasrazide after diagnosis,and the dose was gradually increased to obtain the best effect.The children were followed up for 1.5~3 years,and the current maximum dose of the drug was 20~25 mg/(kg·d).All the children recovered basically.At present,the dosage of dosilazine in case 4 was 12 mg/(kg·d),and dystonia was still present when agitated,and the dosage was continued to be increased slowly.Conclusion The symptoms of DRD are not special in infants.Genetic tests should be performed as soon as possible,and the treatment effect of doserazine is good.