Romani Cristina, Palermo Liana, MacDonald Anita, Limback Ellie, Hall S Kate, Geberhiwot Tarekegn
School of Life and Health Sciences, Aston University.
Birmingham Children's Hospital.
Neuropsychology. 2017 Mar;31(3):242-254. doi: 10.1037/neu0000336.
Phenylketonuria (PKU) is due to an inability to metabolize the amino acid phenylalanine (Phe), leading to its accumulation in the brain. Phe levels can be controlled following a protein-free diet, but cognitive impairments are still present. A number of questions remain to be answered related to which type of metabolic control is important, the age when it is important, the cognitive functions which are most affected and, the best tests to use to monitor cognitive health.
We investigated the impact of metabolic control at different ages on cognitive performance in 37 early treated adults with PKU.
(a) Phe variation was as associated to performance as average Phe showing that stable dietary control is as important as strict control; (b) For some tasks, current and adult Phe were stronger predictors of performance than childhood or adolescent Phe, showing the importance of a strict diet even in adulthood; and (c) The relationship between performance and Phe levels varied depending on time and cognitive domain. For some functions (sustained attention, visuomotor coordination), Phe at the time of testing was the best predictor. While for other functions (visual attention, executive functions) there was a diminishing or stable relationship across time.
Results show the importance of selecting the right tasks to monitor outcomes across ages, but also that the impact of bio-chemical disruptions is different for different functions, at different ages. We show how inherited metabolic diseases offer us a unique vantage point to inform our understanding of brain development and functioning. (PsycINFO Database Record
苯丙酮尿症（PKU）是由于无法代谢氨基酸苯丙氨酸（Phe），导致其在大脑中蓄积。遵循无蛋白饮食可控制苯丙氨酸水平，但认知障碍仍然存在。关于哪种类型的代谢控制很重要、在什么年龄重要、哪些认知功能受影响最大以及用于监测认知健康的最佳测试等问题仍有待解答。
我们调查了不同年龄的代谢控制对37名早期接受治疗的苯丙酮尿症成年患者认知表现的影响。
（a）苯丙氨酸变化与表现的关联程度与平均苯丙氨酸水平相当，表明稳定的饮食控制与严格控制同样重要；（b）对于某些任务，当前和成年期的苯丙氨酸水平比儿童期或青少年期的苯丙氨酸水平更能预测表现，表明即使在成年期严格饮食也很重要；（c）表现与苯丙氨酸水平之间的关系因时间和认知领域而异。对于某些功能（持续注意力、视觉运动协调），测试时的苯丙氨酸是最佳预测指标。而对于其他功能（视觉注意力、执行功能），随着时间推移关系减弱或保持稳定。
结果表明选择合适的任务来监测不同年龄段结果的重要性，同时也表明生化紊乱对不同功能、在不同年龄的影响是不同的。我们展示了遗传性代谢疾病如何为我们理解大脑发育和功能提供独特的有利视角。（PsycINFO数据库记录）
