Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, Republic of China.
Pediatr Neurol. 2012 Feb;46(2):77-82. doi: 10.1016/j.pediatrneurol.2011.11.012.
We analyzed the clinical manifestations, genetic mutations, treatment responses to L-dopa, and long-term neurologic outcomes in Taiwanese infants with tyrosine hydroxylase deficiency. From 1999 to May 2011, we enrolled six infants who had been diagnosed with tyrosine hydroxylase deficiency by identifying point mutations on the tyrosine hydroxylase gene. Two patients manifested fetal distress during the perinatal period. Four patients exhibited generalized tremor as their first observed neurologic sign at age 3 months. All presented brisk reflexes, hypokinesia, rigidity, distal chorea, and athetosis. We identified a novel missense mutation, I382T, and report on the first patient, to the best of our knowledge, with a homozygous R153X nonsense mutation. Five of six patients responded to L-dopa at a dose of 4.2-34.7 mg/kg/day combined with biperiden or selegiline or both. Long-term neurologic outcomes (median follow-up, 5 years and 10.5 months) revealed two patients demonstrated slightly low intelligence quotients, three demonstrated mild to moderate psychomotor retardation, and one died of respiratory failure. A higher dose of L-dopa, together with alternative therapies, may lead to improvements in motor function. However, several years of observation may be needed to reach definitive conclusions about neurologic outcomes.
我们分析了台湾酪氨酸羟化酶缺乏症婴儿的临床表现、基因突变、对左旋多巴的治疗反应和长期神经学结局。从 1999 年到 2011 年 5 月，我们共纳入了 6 名经酪氨酸羟化酶基因点突变鉴定为酪氨酸羟化酶缺乏症的婴儿。有 2 名患者在围产期出现胎儿窘迫。有 4 名患者在 3 个月时出现全身性震颤，为首次观察到的神经症状。所有患者均表现为反射亢进、运动减少、僵硬、远端舞蹈样动作和手足徐动症。我们发现了一种新的错义突变 I382T，并报告了首例患者，据我们所知，患者携带纯合的 R153X 无义突变。6 名患者中有 5 名对左旋多巴的剂量为 4.2-34.7mg/kg/天联合苯海索或司来吉兰或两者联合治疗有反应。长期神经学结局（中位随访 5 年 10.5 个月）显示，2 名患者智力略低，3 名患者轻度至中度精神运动发育迟缓，1 名患者死于呼吸衰竭。较高剂量的左旋多巴联合替代疗法可能会改善运动功能。然而，可能需要数年的观察才能对神经学结局得出明确的结论。
