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

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 − 0.44 for all functions taken together, and − 0.60 for IQ, both highly significant. Separate, significant impairments were found for most functions, but with great variability (ESs from −1.02 to −0.18). 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.