BackgroundThe risk of neuropsychological disorders appears to be high in hyperphenylalaninemia (HPA). The hypothesis of executive function impairment is prominent in accounting for the neuropsychological phenotype in phenylketonuria (PKU) and is suspected in moderate hyperphenylalaninemia (MHP). However, the issue of early onset of executive disorders remains. The aim of this study was to explore the hypothesis of early executive dysfunction in HPA patients and the possible links with certain metabolic variables according to the new international classifications for patients with PKU and MHP. A group of 23 HPA children (12 PKU, 11 MHP) aged 3 to 5 years was included and compared to 50 control children. The two groups were comparable in terms of socio-demographics (age, sex, parental education level). Executive functions were assessed using performance-based tests and daily life questionnaires (parents and teachers).ResultsPreschool HPA patients have comparable executive scores to control subjects. In contrast, PKU patients score significantly worse than MHP patients on 3 executive tests (verbal working memory, visual working memory and cognitive inhibition. There is no executive complaints in daily life (parents and teachers) for the 2 groups of patients. In addition, 3 correlations were identified between executive scores and Phe levels at inclusion, mean Phe level and variability of Phe levels throughout life.ConclusionsThus, there appears to be evidence of early executive dysfunction in PKU preschool-children, but not in MHP children. Occasionally, certain metabolic indicators can predict executive difficulties in young children with PKU.