Abstract

OBJECTIVE: This systematic review aims to analyze the assessment tools used to evaluate executive functions, adaptive skills, and emotional and behavioral outcomes in pediatric and adult patients with phenylketonuria (PKU). Given the impact of elevated phenylalanine (Phe) levels on cognitive and psychological development, this review seeks to provide a comprehensive overview of validated instruments employed in the literature to assess neurocognitive and psychosocial functioning.

MATERIALS AND METHODS: A systematic literature search was conducted according to the PRISMA guidelines. Studies published between 2020 and 2025 were identified through PubMed using keywords related to PKU, executive functions, and cognitive functions. Inclusion criteria encompassed studies focusing on pediatric (0-18 years) and adult PKU patients and using standardized neuropsychological, behavioral, and emotional assessment tools. Studies that did not use standardized tools, as well as reviews, meta-analyses, case reports, and expert opinions, were excluded. Data extraction was performed independently by two reviewers, with discrepancies resolved by consensus.

RESULTS: A total of 168 studies were initially identified. After removing duplicates and applying inclusion criteria, 35 studies were included: 11 studies assessed pediatric patients, 22 focused on adults, and two examined both populations. The most frequently used tools for executive function assessment included the Behavior Rating Inventory of Executive Function, The Developmental Neuropsychological Assessment - II (NEPSY-II), Trail Making Test, and Wechsler Intelligence Scale subtests. Behavioral and emotional functioning were primarily assessed using the Child Behavior Checklist and the Hospital Anxiety and Depression Scale. The review highlighted variability in assessment methodologies, with a lack of standardized protocols across studies.

CONCLUSIONS: The findings underscore the need for a standardized, comprehensive battery of neurocognitive and behavioral assessments tailored to PKU patients across different age groups. Consistent evaluation tools are crucial for monitoring disease progression and treatment outcomes, especially with emerging therapeutic options. Future research should focus on validating existing instruments and developing sensitive measures to assess the quality of life and psychosocial functioning in PKU patients.