Division of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
J Inherit Metab Dis. 2020 Mar;43(2):189-199. doi: 10.1002/jimd.12151. Epub 2019 Aug 20.
In phenylketonuria (PKU) patients, early diagnosis by neonatal screening and immediate institution of a phenylalanine-restricted diet can prevent severe intellectual impairment. Nevertheless, outcome remains suboptimal in some patients asking for additional treatment strategies. Tetrahydrobiopterin (BH ) could be one of those treatment options, as it may not only increase residual phenylalanine hydroxylase activity in BH -responsive PKU patients, but possibly also directly improves neurocognitive functioning in both BH -responsive and BH -unresponsive PKU patients. In the present review, we aim to further define the theoretical working mechanisms by which BH might directly influence neurocognitive functioning in PKU having passed the blood-brain barrier. Further research should investigate which of these mechanisms are actually involved, and should contribute to the development of an optimal BH treatment regimen to directly improve neurocognitive functioning in PKU. Such possible repurposing approach of BH treatment in PKU may improve neuropsychological outcome and mental health in both BH -responsive and BH -unresponsive PKU patients.
在苯丙酮尿症（PKU）患者中，通过新生儿筛查及早诊断，并立即采用限制苯丙氨酸的饮食，可以预防严重的智力障碍。然而，一些患者仍需要额外的治疗策略，因此治疗效果并不理想。四氢生物蝶呤（BH ）可能是其中一种治疗选择，因为它不仅可以增加 BH 反应性 PKU 患者中残留的苯丙氨酸羟化酶活性，而且可能直接改善 BH 反应性和 BH 非反应性 PKU 患者的神经认知功能。在本综述中，我们旨在进一步明确 BH 通过血脑屏障直接影响 PKU 神经认知功能的理论作用机制。进一步的研究应该调查哪些机制实际上参与其中，并有助于制定最佳的 BH 治疗方案，以直接改善 PKU 的神经认知功能。这种 BH 在 PKU 中的可能的重新定位治疗方法可能会改善 BH 反应性和 BH 非反应性 PKU 患者的神经心理结局和心理健康。
