Executive Functions and Long-Term Metabolic Control in Adults with Phenylketonuria (PKU)

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.