Department of Psychological Sciences, University of Missouri, Columbia, MO, United States.
Department of Child Health, University of Missouri School of Medicine, Columbia, MO, United States.
Neuroimage Clin. 2013 Aug 30;3:539-47. doi: 10.1016/j.nicl.2013.08.012. eCollection 2013.
Phenylketonuria (PKU) is a rare genetic condition characterized by an absence or mutation of the PAH enzyme, which is necessary for the metabolism of the amino acid phenylalanine into tyrosine. Recently, sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), has been introduced as a supplemental treatment to dietary phe control for PKU. Very little is known regarding BH4 treatment and its effect on brain and cognition. The present study represents the first examination of potential changes in neural activation in patients with PKU during BH4 treatment. To this end, we utilized an n-back working memory task in conjunction with functional magnetic resonance imaging (fMRI) to evaluate functional brain integrity in a sample of individuals with PKU at three timepoints: Just prior to BH4 treatment, after 4 weeks of treatment, and after 6 months of treatment. Neural activation patterns observed for the PKU treatment group were compared with those of a demographically-matched sample of healthy non-PKU individuals who were assessed at identical time intervals. Consistent with past research, baseline evaluation revealed impaired working memory and atypical brain activation in the PKU group as compared to the non-PKU group. Most importantly, BH4 treatment was associated with improvements in both working memory and brain activation, with neural changes evident earlier (4-week timepoint) than changes in working memory performance (6-month timepoint).
苯丙酮尿症（PKU）是一种罕见的遗传疾病，其特征是缺乏或突变 PAH 酶，该酶对于将氨基酸苯丙氨酸代谢为酪氨酸是必需的。最近，二盐酸沙丙蝶呤（BH4 的合成形式）已被引入作为 PKU 患者饮食 phe 控制的补充治疗。关于 BH4 治疗及其对大脑和认知的影响，人们知之甚少。本研究代表了首次检查 PKU 患者在 BH4 治疗期间神经激活的潜在变化。为此，我们利用 n-back 工作记忆任务结合功能磁共振成像（fMRI），在三个时间点评估了 PKU 患者样本的大脑功能完整性：在 BH4 治疗之前、治疗 4 周后和治疗 6 个月后。将 PKU 治疗组的神经激活模式与在相同时间间隔接受评估的具有匹配人口统计学特征的健康非 PKU 个体的样本进行比较。与过去的研究一致，基线评估显示与非 PKU 组相比，PKU 组的工作记忆和异常大脑激活受损。最重要的是，BH4 治疗与工作记忆和大脑激活的改善有关，神经变化比工作记忆表现的变化更早（4 周时间点）。
