Meta-analysis of cognitive outcomes in children and adults with early treated phenylketonuria – Results across functions

Meta-analyses were used to track cognitive outcomes in early treated people with phenylketonuria. We compared impairment sizes and possible modulations by blood Phe in young adults and children/early adolescents.

We identified results for 29 adult PKU groups and 21 child groups (N-participants = 904 and 460; mean age 27 and 11 years; mean current blood Phe: 1010; and 527; median 899 and 494; SD= =396 and 159) with 278 separate outcome measures available for adults and 175 for children.

Results demonstrated a similar overall level of impairment across ages, corresponding to approximately 0.5 of a standard deviation difference from controls. However, children showed more homogeneous impairments across functions compared to adults who showed a larger difference between the most and least impaired measures and a stronger difference of impairment between speed measures (impaired) and accuracy measures (preserved). In both age groups, blood Phe level modulated the effect size of the impairment in several conditions, but speed of processing appeared to be affected more by childhood levels than current adult levels consistent with previous results.

Results indicate that negative effects of PKU persist across the lifespan, but that adults with PKU may rely on relatively unaffected learning skills and on prioritization of resources to achieve good accuracy and good performance in tasks tapping crystallized intelligence, even if speed remains impaired. This has positive implications for educational and employment prospects, but it is unclear how positive trends generalize to the whole PKU population beyond groups engaged in research.