Tomm Anne, Thiele Alena G, Rohde Carmen, Schlögl Haiko, Kiess Wieland, Beblo Skadi
Center for Pediatric Research Leipzig, Department of Women and Child Health, Hospital for Children and Adolescents, University Hospital Leipzig, 04103 Leipzig, Germany.
Department of Internal Medicine, Section of Endocrinology, Nephrology, Rheumatology, University Hospital Leipzig, 04103 Leipzig, Germany.
Metabolites. 2025 Mar 12;15(3):197. doi: 10.3390/metabo15030197.
Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by phenylalanine hydroxylase deficiency, resulting in highly elevated blood phenylalanine (Phe) concentrations, leading to neurotoxic effects. Despite advancements in treatment, adult patients with PKU may experience impairments in executive functions (EFs). This study investigates the influence of metabolic control across different life stages on EFs and sociodemographic outcomes in adult PKU. We conducted a monocentric study with 36 early-diagnosed and treated PKU patients (mean age: 34.8 years). EFs were assessed using the Test Battery for Attentional Performance (TAP) and the Tower of London (TL-D). Metabolic data were extracted from medical records, focusing on childhood and adulthood metabolic control, including Phe fluctuations. Sociodemographic data were collected via questionnaires. Statistical analyses explored relationships between EFs, metabolic control, and sociodemographic data. EFs in the cohort were within the lower average range. Significant negative correlations could be observed between EF performance and dried blood Phe concentrations during childhood (ages 0-10 years) as well as current Phe concentrations and Phe variation. Elevated childhood Phe concentrations were associated with lower educational attainment. Sociodemographic characteristics, such as employment status and living arrangements, aligned with those of the general population. Optimal cognitive development in PKU requires good metabolic control, particularly in early childhood. In adulthood, while dietary restrictions may be relaxed, maintaining low and stable Phe concentrations is crucial for EFs. Consistent monitoring and tailored therapeutic approaches throughout life seem essential for optimizing metabolic and neurocognitive outcome in PKU.
苯丙酮尿症（PKU）是一种罕见的遗传性代谢紊乱疾病，由苯丙氨酸羟化酶缺乏引起，导致血液中苯丙氨酸（Phe）浓度大幅升高，进而产生神经毒性作用。尽管在治疗方面取得了进展，但成年PKU患者可能仍存在执行功能（EFs）受损的情况。本研究调查了不同生命阶段的代谢控制对成年PKU患者的EFs和社会人口学结果的影响。我们进行了一项单中心研究，纳入了36例早诊断并接受治疗的PKU患者（平均年龄：34.8岁）。使用注意力表现测试电池（TAP）和伦敦塔测试（TL-D）评估EFs。从医疗记录中提取代谢数据，重点关注儿童期和成年期的代谢控制，包括Phe波动情况。通过问卷调查收集社会人口学数据。统计分析探讨了EFs、代谢控制和社会人口学数据之间的关系。该队列中的EFs处于较低平均水平范围内。在儿童期（0至10岁），EF表现与干血Phe浓度之间以及当前Phe浓度和Phe变异之间可观察到显著的负相关。儿童期Phe浓度升高与较低的教育程度相关。社会人口学特征，如就业状况和生活安排，与一般人群的特征相符。PKU患者的最佳认知发展需要良好的代谢控制，尤其是在幼儿期。在成年期，虽然饮食限制可能会放宽，但维持低且稳定的Phe浓度对EFs至关重要。在整个生命过程中持续监测和量身定制治疗方法对于优化PKU患者的代谢和神经认知结果似乎至关重要。
