Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC
Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC
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DOI：
10.1007/s10545-011-9394-5
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发表时间：
2012-03-01
影响因子：
4.2
通讯作者：
Spiekerkoetter, Ute
中科院分区：
文献类型：
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作者：
Thimm, Eva;Richter-Werkle, Renate;Spiekerkoetter, Ute
NTBC治疗I型高酪氨酸血症（HT I）通过预防急性肝功能衰竭和肝细胞癌大大提高了生存率。然而，血浆酪氨酸浓度升高的患者有认知障碍的首次报道。在此，我们使用标准化的心理测试来评估9名长期接受NTBC治疗的早期治疗的hti患者在认知、运动能力和语言方面的神经认知发展。高血浆酪氨酸浓度经常导致9例患者中有7例12个月血浆酪氨酸中位浓度升高。血浆NTBC浓度一般在较低的治疗范围内。7名3岁以上患者中有5名（71%）的总智商得分低于平均水平。此外，7例3岁以上患者中有5例出现不均匀的测试特征，不同测试量表之间存在显著差异。七名患者中有四名（57%）的运动能力低于正常水平。脑MRI未见异常。学龄儿童的语音学评估记录了除1例（80%）外的所有测试患者的语言发育障碍或迟缓，然而，除1例患者外，所有患者都有移民背景。大量患者在发育、运动功能和言语评估中表现低于正常水平。我们认为智力障碍是hti型患者在NTBC治疗下血浆酪氨酸升高的长期并发症，这在其他高酪氨酸血症中也有观察到。这些发现仍有待在更多患者中得到证实。
The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations.We here assess the neurocognitive development using standardized psychometric test batteries with respect to cognition, motor abilities and speech in nine early-treated patients with HT I under long-term NTBC treatment.High plasma tyrosine concentrations were frequently documented resulting in elevated 12-month median plasma tyrosine concentrations in seven out of nine patients. Plasma NTBC concentrations were generally in the lower therapeutic range. Five out of seven patients (71%) above 3 years of age had a total IQ score below the average. In addition, five out of seven patients above 3 years showed an inhomogenous test profile with significant differences between the different testing scales. Motor abilities were subnormal in four out of seven patients(57%). Cerebral MRI revealed no abnormalities. Logopedic evaluation in children at school age documented dysfunction or retardation in language development in all but one of the tested patients (80%), however, all but one patients had a migration background.A high number of patients performed below normal in the assessment of development, motor function and speech. We propose intellectual impairment as long-term complication in HT type I with elevated plasma tyrosine under NTBC treatment as observed in other hypertyrosinemias. These findings remain to be reproduced in greater patient numbers.