摘要
目的探讨酪氨酸羟化酶缺乏症所致多巴反应性肌张力不全附加症的诊疗策略。方法回顾性分析2018年10月至2020年7月于北京大学第一医院就诊的9例婴儿期起病酪氨酸羟化酶缺乏症患者,分析其临床表型、编码酪氨酸羟化酶的TH基因及左旋多巴疗效。结果9例患者在5.5个月以内起病,7例(77.8%)表现为重型婴儿帕金森综合征伴运动发育迟缓,2例(22.2%)表现为极重型进行性婴儿脑病。患者均携带TH基因纯合或复合杂合变异。共发现TH基因变异12种(10个错义变异,1个剪切点变异),1个新变异(外显子9-11缺失),p.R233H(33.3%)变异最常见。经左旋多巴治疗,7例症状明显改善,但精细动作仍欠协调;2例脑病患者左旋多巴加量困难,药物不耐受,症状改善不明显,伴严重的智力运动发育迟缓和营养不良。结论酪氨酸羟化酶缺乏症引起多巴反应性肌张力不全附加症重型患者预后相对较好,婴儿脑病患者症状重,左旋多巴加量困难,预后差。
Objective To investigate the strategy of diagnosis and treatment of dopa responsive dystonia-plus(DRD-plus)due to tyrosine hydroxylase deficiency.Methods Nine patients with DRD-plus and onset in infancy treated in our hospital from October 2018 to July 2020 were retrospectively analyzed.Its clinical phenotype,TH gene encoding tyrosine hydroxylase,and efficacy of levodopa were analyzed.Results Nine patients developed the disease within 5.5 months old.Seven cases(77.8%)presented with severe infantile Parkinsonism syndrome accompanied by delayed motor development.Two patients(22.2%)presented with progressive infantile encephalopathy.All the patients had complex heterozygous or homozygous variants of TH gene.A total of 12 variations of TH gene(10 missense variations and 1 splice site variations)and one new variation(exon 9-11 deletion)were identified.p.R233H(33.3%)was the most common variation.After treatment with levodopa,7 cases showed significant improvement in symptoms,but poor coordination in fine motor skills.Two cases with infantile encephalopathy were intolerant to the drug.They had difficulty in increasing the dosage of levodopa.They showed little improvement in symptoms,and suffered from severe intellectual and motor developmental delays and malnutrition.Conclusions Patients with severe DRD-plus caused by tyrosine hydroxylase deficiency have a relatively good prognosis.However,patients with infantile encephalopathy have difficulty in increasing the dosage of levodopa.They have a poor prognosis.
作者
张尧
董慧
张会婷
张婧韬
马未萌
杨艳玲
ZHANG Yao;DONG Hui;ZHANG Hui-ting;ZHANG Jing-tao;MA Wei-meng;YANG Yan-ling(Children's Medical Center,Peking University First Hospital,Beijing 102600,China)
出处
《实用医院临床杂志》
2026年第1期16-19,共4页
Practical Journal of Clinical Medicine
基金
国家重点研发计划(编号:2022YFC2703603)
国家自然科学基金资助项目(编号:62473004)。
