Abstract:
Considering the cognitive, behavioural and quality of life consequences of high phenylalanine
levels in early-treated phenylketonuria (PKU), this study sought to provide initial support for
whether the monitoring and active management of individuals with mild, non-PKU
hyperphenylalaninemia (MHP), similar to those with PKU, would be advisable. We compared
six individuals aged 6 to 15 with untreated MHP (birth Phe <400μmol/L), with six age- and
gender-matched individuals with early-treated PKU (birth Phe >400μmol/L), and six healthy,
matched controls across measures of cognition, executive function, behaviour and quality of
life. Participants completed the Wechsler Intelligence Scale for Children–5th edition, Wechsler
Individual Achievement Test– 2nd edition, Australian, Abbr., Trail-Making test, Contingency
Naming Test and Oral Fluency test. Self- and parent-report rating scales administered included
the Conners Comprehensive Behavior Rating Scales, Behavior Rating Inventory of Executive
Function-2nd edition, and Pediatric Quality of Life questionnaires, with PKU participants
additionally completing the Phenylketonuria-Quality of Life questionnaires. Early-treated PKU
participants demonstrated normal intelligence, pointing to the efficacy of dietary management.
Quality of life and behavioural difficulties were observed (in the absence of significant cognitive
deficits) including more severe externalising problems; observed at rates eight times that seen
in the normal population. MHP participants also exhibited normal intellectual ability. They
performed more poorly on working memory relative to other indices, however differences were
not statistically significant. Quality of life and behaviour was in keeping with controls or slightly
poorer than controls (though not significantly different), but not so severe as that seen in the
PKU group. For MHP and PKU participants, higher phenylalanine was associated with lower
ability and achievement, and higher rates of behavioural and emotional difficulties. This study
adds to the literature on the prevalence and outcomes of the phenotypic variants of HPA. MHP
made up 19.2% of total cases (1:87,726 births), and PKU 80.8% of total cases (1/20,887 births)
in New Zealand. Whilst power was limited by the small sample, this study importantly provides
information on cognition, behaviour, and quality of life in a sample of MHP participants
previously undescribed in the literature.