Meta-analyses of cognitive functions in early-treated adults with phenylketonuria

Cristina Romani, Andrew Olson, Lynne Aitkenhead, Lucy Baker, Dhanesha Patel, Francjan Van Spronsen, Anita MacDonald, Annemiek van Wegberg, Stephan Huijbregts

Research output: Contribution to journalReview articlepeer-review


Our study estimated size of impairment for different cognitive functions in early-treated adults with PKU (AwPKU) by combining literature results in a meta-analytic way. We analysed a large set of functions (N=19), each probed by different measures (average=12). Data were extracted from 26 PKU groups and matched controls, with 757 AwPKU contributing 220 measures. Effect sizes (ESs) were computed using Glass' ∆ where differences in performance between clinical/PKU and control groups are standardized using the mean and standard deviation of the control groups. Significance was assessed using 'measures nested within independent PKU groups' as a random factor. The weighted Glass' ∆ was -.44 for all functions taken together, and -.60 for IQ, both highly significant. Separate, significant impairments were found for most functions, but with great variability (ESs from -1.02 to -.18). The most severe impairments were in reasoning, visual-spatial attention speed, sustained attention, visuo-motor control, and flexibility. Effect sizes were larger with speed than accuracy measures, and with visuo-spatial than verbal stimuli. Results show a specific PKU profile that needs consideration when monitoring the disease.

Original languageEnglish
Article number104925
Number of pages18
JournalNeuroscience and Biobehavioral Reviews
Early online date22 Oct 2022
Publication statusPublished - Dec 2022

Bibliographical note

Copyright © 2022, The Authors. This is an open access article under the CC BY license (


  • PKU
  • Patterna of cognitive impairments
  • Metabolic disease
  • Executive functions
  • Memory
  • Language
  • Speed and accuracy
  • Verbal vs Visual


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