Department of General Pediatrics, Medical Faculty, University Dusseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
J Inherit Metab Dis. 2012 Mar;35(2):263-8. doi: 10.1007/s10545-011-9394-5. Epub 2011 Nov 9.
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.
NTBC 在 I 型高酪氨酸血症（HT I）治疗中的应用，通过预防急性肝功能衰竭和肝细胞癌，极大地提高了患者的生存率。然而，有报道称，在血浆酪氨酸浓度升高的患者中，存在认知障碍。
我们在此评估了 9 名接受长期 NTBC 治疗的 HT I 早期患者的神经认知发育情况，使用标准化心理计量测试量表评估认知、运动能力和言语。
经常记录到高血浆酪氨酸浓度，导致 9 名患者中有 7 名患者在 12 个月时的血浆酪氨酸浓度中位数升高。血浆 NTBC 浓度通常处于较低的治疗范围。7 名年龄超过 3 岁的患者中有 5 名（71%）的总智商得分低于平均值。此外，7 名年龄超过 3 岁的患者中有 5 名表现出不均匀的测试模式，不同测试量表之间存在显著差异。7 名患者中有 4 名（57%）的运动能力异常。脑部 MRI 无异常。在学龄儿童中进行的语言评估显示，除了一名患者（80%）外，所有接受测试的患者均存在语言发育功能障碍或迟缓，但所有患者除了一名之外均有移民背景。
在发展、运动功能和言语方面，大量患者表现异常。我们提出，在 NTBC 治疗下，血浆酪氨酸升高的 HT I 型患者存在智力障碍，这是一种长期并发症，正如在其他高酪氨酸血症中观察到的那样。这些发现需要在更大的患者数量中进行验证。
