BACKGROUND Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and dietary phenylalanine and tyrosine restriction improves physical health and life expectancy in Tyrosinemia type 1 (TT1). However, neurocognitive outcome is suboptimal. This study aimed to investigate behavior problems and health-related quality of life (HR-QoL) in NTBC-dietary-treated TT1 and to relate this to phenylalanine and tyrosine concentrations. RESULTS Thirty-one TT1 patients (19 males; mean age 13.9 ± 5.3 years) were included in this study. Emotional and behavioral problems, as measured by the Achenbach System of Empirically Based Assessment, were present in almost all domains. Attention and thought problems were particularly evident. HR-QoL was assessed by the TNO AZL Children's and Adults QoL questionnaires. Poorer HR-QoL as compared to reference populations was observed for the domains: independent daily functioning, cognitive functioning and school performance, social contacts, motor functioning, and vitality. Both internalizing and externalizing behavior problems were associated with low phenylalanine (and associated lower tyrosine) concentrations during the first year of life. In contrast, high tyrosine (and associated higher phenylalanine) concentrations during life and specifically the last year before testing were associated with more internalizing behavior and/or HR-QoL problems. CONCLUSIONS TT1 patients showed several behavior problems and a lower HR-QoL. Associations with metabolic control differed for different age periods. This suggests the need for continuous fine-tuning and monitoring of dietary treatment to keep phenylalanine and tyrosine concentrations within target ranges in NTBC-treated TT1 patients.

中文翻译：

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NTBC治疗的1型酪氨酸血症患者的情绪和行为问题，生活质量和代谢控制。

背景技术用2-（2-硝基-4-三氟甲基苯甲酰基）-1，3-环己二酮（NTBC）以及饮食中的苯丙氨酸和酪氨酸限制治疗可改善1型酪氨酸血症（TT1）的身体健康和预期寿命。但是，神经认知结果并不理想。这项研究旨在调查NTBC饮食处理的TT1中的行为问题和与健康相关的生活质量（HR-QoL），并将其与苯丙氨酸和酪氨酸浓度相关联。结果本研究共纳入31例TT1患者（男19例；平均年龄13.9±5.3岁）。通过基于经验的评估的Achenbach系统测得的情绪和行为问题几乎存在于所有领域。注意和思想问题特别明显。通过TNO AZL儿童和成人QoL问卷对HR-QoL进行评估。在以下方面，与参考人群相比，HR-QoL较差：独立的日常功能，认知功能和学校成绩，社交联系，运动功能和活力。在生命的第一年内，内在化和外在化行为问题都与低苯丙氨酸（和相关的较低酪氨酸）浓度有关。相比之下，一生中，尤其是测试前的最后一年中，较高的酪氨酸浓度（以及相关的较高的苯丙氨酸浓度）与更多的内化行为和/或HR-QoL问题有关。结论TT1患者表现出一些行为问题和较低的HR-QoL。不同年龄段与代谢控制的关联也不同。