Department of Human Genetics, Emory University School of Medicine, 101 Woodruff Circle, Suite 7130, Atlanta, GA, 30322, USA.
Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
Orphanet J Rare Dis. 2023 Jul 29;18(1):222. doi: 10.1186/s13023-023-02842-y.
Despite early diagnosis and compliance with phenylalanine (Phe)-restricted diets, many individuals with phenylketonuria (PKU) still exhibit neurological changes and experience deficits in working memory and other executive functions. Suboptimal choline intake may contribute to these impairments, but this relationship has not been previously investigated in PKU. The objective of this study was to determine if choline intake is correlated with working memory performance, and if this relationship is modified by diagnosis and metabolic control.
This was a cross-sectional study that included 40 adults with PKU and 40 demographically matched healthy adults. Web-based neurocognitive tests were used to assess working memory performance and 3-day dietary records were collected to evaluate nutrient intake. Recent and historical blood Phe concentrations were collected as measures of metabolic control.
Working memory performance was 0.32 z-scores (95% CI 0.06, 0.58) lower, on average, in participants with PKU compared to participants without PKU, and this difference was not modified by total choline intake (F[1,75] = 0.85, p = 0.36). However, in a subgroup with complete historical blood Phe data, increased total choline intake was related to improved working memory outcomes among participants with well controlled PKU (Phe = 360 µmol/L) after adjusting for intellectual ability and mid-childhood Phe concentrations (average change in working memory per 100 mg change in choline = 0.11; 95% CI 0.02, 0.20; p = 0.02). There also was a trend, albeit nonsignificant (p = 0.10), for this association to be attenuated with increased Phe concentrations.
Clinical monitoring of choline intake is essential for all individuals with PKU but may have important implications for working memory functioning among patients with good metabolic control. Results from this study should be confirmed in a larger controlled trial in people living with PKU.
尽管早期诊断和遵循苯丙氨酸（Phe）限制饮食，许多苯丙酮尿症（PKU）患者仍表现出神经变化，并在工作记忆和其他执行功能方面存在缺陷。胆碱摄入不足可能导致这些损伤，但以前尚未在 PKU 中研究过这种关系。本研究的目的是确定胆碱摄入是否与工作记忆表现相关，以及这种关系是否受诊断和代谢控制的影响。
这是一项横断面研究，包括 40 名 PKU 成年患者和 40 名在人口统计学上匹配的健康成年人。使用基于网络的神经认知测试评估工作记忆表现，并收集 3 天的饮食记录以评估营养素摄入。最近和历史上的血液 Phe 浓度被收集作为代谢控制的衡量标准。
与无 PKU 参与者相比，PKU 参与者的工作记忆表现平均低 0.32 个 z 分数（95%置信区间 0.06，0.58），而总胆碱摄入量并不能改变这种差异（F[1,75] = 0.85，p = 0.36）。然而，在具有完整历史血液 Phe 数据的亚组中，在调整智力能力和儿童中期 Phe 浓度后，总胆碱摄入量的增加与 PKU 控制良好的参与者的工作记忆结果改善相关（每 100mg 胆碱变化时工作记忆的平均变化为 0.11；95%置信区间 0.02，0.20；p = 0.02）。虽然这种关联存在趋势，但无统计学意义（p = 0.10），随着 Phe 浓度的增加，这种关联趋于减弱。
对所有 PKU 患者进行胆碱摄入的临床监测至关重要，但对于代谢控制良好的患者的工作记忆功能可能具有重要意义。本研究的结果应在 PKU 患者的更大规模对照试验中得到证实。
