BLOOD TYROSINE LEVELS WITH TYROSINE SUPPLEMENTATION IN PHENYLKETONURIA

由于常规的新生儿筛查和对这种疾病的早期饮食治疗，苯丙酮尿症引起的精神发育迟滞基本上已经消除。 然而，在早期治疗的儿童中，神经心理和情感缺陷的频率很高。 越来越多的证据表明，这些困难中有许多是由于高级功能（所谓的执行功能）的缺陷造成的。 由于执行功能似乎是由前额叶皮质控制的，并且由于前额叶皮质具有大脑中最高水平的多巴胺周转，因此使其对多巴胺的减少特别敏感，并且由于多巴胺是酪氨酸的代谢物，因此已经假设执行功能缺陷是由于大脑酪氨酸不足。本研究的目的是确定在苯丙氨酸限制饮食治疗的苯丙酮尿症（PKU）儿童和年轻成人中补充L-酪氨酸对血液酪氨酸的反应。 如果发现拟给予的大于通常量的L-酪氨酸补充剂确实产生显著和持续的血液酪氨酸反应，而不显著增加酪氨酸代谢物的积累，则可以考虑这种比2-（2-硝基-4-氟甲基苯甲酰基）-1，3环己烷二酮（NTBC）便宜得多的治疗。

Mental retardation from PKU has essentially been eliminated due to routine newborn screening and early dietary treatment of this disease. However, there is a high frequency of neuropsychological and emotional deficits among the early treated children. There is a growing body of evidence that many of these difficulties result from deficits in higher function, so called executive function. Since executive function seems to be controlled by the prefrontal cortex, and since the prefrontal cortex has one of the highest levels of dopamine turnover in the brain, thus making it especially sensitive to reductions in dopamine, and since dopamine is a metabolite of tyrosine, it has been hypothesized that the executive function deficits result from insufficient brain tyrosine. The objective of this study is to determine the blood tyrosine response to L-tyrosine supplementation in children and young adults with phenylketonuria (PKU) who are on phenylalanine restricted dietary treatment. Should it be found that the larger than usual amount of L-tyrosine supplementation proposed to be given does produce a marked and sustained blood tyrosine response without markedly increasing the accumulation of tyrosine metabolites, this treatment, which is much less expensive than 2-(2-nitro-4-fluoromethylbenzoyl)-1,3 cyclohexanedione(NTBC), could be considered.