Biochemical markers associated with executive function in adolescents with early and continuously treated Phenylketonuria (ECT-PKU)

Abstract

Debate continues as to whether executive function (EF), develop normally in children with PKU. Using a mixed model, we measured EF in ten adolescent children with PKU and six sibling controls, and examined associations between cognitive function and phenylalanine (phe) as well as the phenylalanine:tyrosine ratio (phe:tyr). Measurements were taken on two occasions anticipated to yield variation in concurrent phe resulting from changes in dietary compliance (i.e. Christmas holiday versus non-holiday period). A repeated measures ANOVA using Behaviour Rating Inventory of Executive Function (BRIEF) scores yielded the following results: no significant interactions; two significant group effects of substantially impaired working memory and initiation skills in children with PKU than controls irrespective of occasion; and, two significant time effects, suggestive of slightly poorer “non-holiday” planning and organisation scores in both PKU and control groups. Further analyses revealed that phe levels were not significantly different at the time occasions we sampled, suggesting that holiday dietary compliance may be better than expected. Correlations between EF and biochemistry in children with PKU showed that the participant’s phe:tyr ratio across their lifetime and particularly prior to age 12 years, demonstrated the greatest number of significant and strong positive correlations across most scales of EF impairment.