Background: Phenylketonuria (PKU) is a rare condition that causes the accumulation of phenylalanine; without prompt diagnosis and treatment following birth, severe neurologic and cognitive impairments occur. While dietary management can help reduce Phe levels, adherence is challenging and deficits in cognitive function often remain. The importance of the exact features of dietary management, treatment, and control at different time points with respect to eventual IQ scores has not been established. The objective of the present study was to review and describe published data on the impact of PKU on cognition as measured by IQ among PKU patients receiving early dietary management.
Methods: A systematic literature review was conducted following PRISMA guidelines to examine IQ among patients with PKU. Instruments used to assess IQ included the Wechsler Intelligence Scale, Culture Fair Intelligence Test and Stanford Binet Test. Results were reported overall and by subgroups.
Results: Twenty-five out of 28 identified studies could be included in the review. Lower IQ scores were generally observed among those with high phenylalanine levels, although variations in the study populations hinder the ability to make comparisons. Mean IQ scores among those with PKU were consistently lower compared to control groups. Even though all patients in this review received early treatment, those with poor dietary adherence and higher phenylalanine levels tended to show poorer cognitive ability.
Conclusions: Cognition is affected in PKU, despite early and continuous dietary management. Treatments are needed that reduce phenylalanine levels so that the burden of neurocognitive impairment in PKU can be alleviated.
Keywords: Adherence; Diet; IQ; PKU; Phenylketonuria.
© 2025. The Author(s).