Abstract
ObjectiveEarly treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills.MethodsNinety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined.ResultsPKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Quality of social skills was negatively related to lifetime phenylalanine levels in adult patients, and specifically to Phe-levels between 0 and 7, and between 8 and 12 years. There were no differences with respect to social outcome measures between the BH4 and non-BH4 groups.ConclusionPKU-patients have Phe-related difficulties with social-cognitive functioning and social skills. Problems seem to be more evident among adolescents and adults with PKU. High Phe-levels during childhood and early adolescence seem to be of greater influence than current and recent Phe-levels for these patients.
Highlights
In phenylketonuria (PKU; OMIM 212600), the brain dysfunction is, at least in part, considered to be the result of dopamine and serotonin deficiency (Blau et al 2010)
Adult patients report difficulties with social skills compared to controls
Higher lifetime rather than concurrent Phe-levels were related to poorer social outcomes
Summary
In phenylketonuria (PKU; OMIM 212600), the brain dysfunction is, at least in part, considered to be the result of dopamine and serotonin deficiency (Blau et al 2010). Dopamine depletion has repeatedly been related to deficits in executive function (EF), which is the most frequently reported cognitive deficit in ET-PKU (Christ et al 2010), and with impairments in social cognition (Skuse and Gallagher 2009). Whereas a Phe-restricted diet with amino acid supplements is still the most widely-used treatment strategy for PKU, a sub-group of patients benefits (at least with respect to keeping Phe-levels in the lower ranges) from the use of tetrahydrobiopterin (BH4), which is a co-factor of the deficient enzyme phenylalanine hydroxylase (PAH). Higher Phe-levels are permitted in many national guidelines, and it is not yet fully clear what the upper target Phe-levels should be in adolescence and adulthood in relation to cognitive ability, social and behavioural functioning, necessitating more research in these age groups
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