School of Psychology, University of Leeds, Leeds, LS2 9JT, UK.
Biochemical Genetics, Specialist Laboratory Medicine, St James's University Hospital, Block 46, Leeds, LS9 7TF, UK.
Orphanet J Rare Dis. 2018 Aug 30;13(1):150. doi: 10.1186/s13023-018-0893-4.
Even though early dietary management of phenylketonuria (PKU) successfully prevents severe neurological impairments, deficits in cognitive functioning are still observed. These deficits are believed to be the result of elevated levels of phenylalanine throughout life. Research on cognitive functioning in adults with PKU (AwPKU) often focuses on domains shown to be compromised in children with PKU, such as attention and executive functions, whereas other cognitive domains have received less attention. This systematic review aimed to provide an overview of cognitive functioning across domains examined in early treated (ET) AwPKU.
A systematic search was performed in Ovid MEDLINE(R), PsycINFO, Web of Science, Cochrane, Scopus, Embase, ScienceDirect, and PubMed for observational studies on cognitive performance in ET AwPKU.
Twenty-two peer-reviewed publications, reporting on outcomes from 16 studies were reviewed. Collectively, the results most consistently showed deficits in vigilance, working memory and motor skills. Deficits in other cognitive domains were less consistently observed or were understudied. Furthermore, despite reports of several associations between cognitive performance and phenylalanine (Phe) levels throughout life the relationship remains unclear. Inconsistencies in findings across studies could be explained by the highly heterogeneous nature of study samples, resulting in large inter- and intra-variability in Phe levels, as well as the use of a variety of tests across cognitive domains, which differ in sensitivity. The long-term cognitive outcomes of early and continuous management of PKU remain unclear.
To better understand the development of cognitive deficits in ET AwPKU, future research would benefit from 1) (inter)national multicentre-studies; 2) more homogeneous study samples; 3) the inclusion of other nutritional measures that might influence cognitive functioning (e.g. Phe fluctuations, Phe:Tyrosine ratio and micronutrients such as vitamin B12); and 4) careful selection of appropriate cognitive tests.
尽管苯丙酮尿症（PKU）的早期饮食管理成功预防了严重的神经损伤，但认知功能仍存在缺陷。这些缺陷被认为是由于一生中苯丙氨酸水平升高所致。对成人 PKU（AwPKU）认知功能的研究通常集中在儿童 PKU 中受影响的领域，如注意力和执行功能，而其他认知领域则受到较少关注。本系统评价旨在概述早期治疗（ET）AwPKU 中检查的各个认知领域的认知功能。
在 Ovid MEDLINE（R）、PsycINFO、Web of Science、Cochrane、Scopus、Embase、ScienceDirect 和 PubMed 中进行了系统搜索，以查找关于 ET AwPKU 认知表现的观察性研究。
共审查了 22 篇同行评议的出版物，其中有 16 项研究的结果。总的来说，结果最一致地表明警觉性、工作记忆和运动技能存在缺陷。在其他认知领域观察到的缺陷较少或研究不足。此外，尽管有报道称在整个生命过程中认知表现与苯丙氨酸（Phe）水平之间存在多种关联，但这种关系仍不清楚。研究之间的结果不一致可以用研究样本的高度异质性来解释，导致 Phe 水平的个体间和个体内变异性很大，以及在不同认知领域使用各种不同敏感性的测试。早期和持续管理 PKU 的长期认知结果仍不清楚。
为了更好地理解 ET AwPKU 中认知缺陷的发展，未来的研究将受益于 1）（国际）多中心研究；2）更同质的研究样本；3）纳入可能影响认知功能的其他营养措施（例如 Phe 波动、Phe：酪氨酸比和微量营养素，如维生素 B12）；4）仔细选择适当的认知测试。
