A lifetime with Phenylketonuria: Towards a better understanding of therapeutic targets

Rianne Jahja

    Research output: ThesisThesis fully internal (DIV)

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    The thesis ‘A lifetime with Phenylketonuria. Towards a better understanding of therapeutic targets’ provides the first findings of the Dutch multicentre Phenylketonuria-COBESO study, conducted between 2012-2015. COBESO stands for the COgnitive, BEhavioural and SOcial issues examined in this study. 108 Patients with phenylketonuria (PKU) from six university medical centres and 112 healthy controls of various ages were included. The objective was to examine cognitive functioning, mental health, social cognitive functioning and social skills of early and continuously treated patients with PKU in relation to their metabolic control (as measured by blood phenylalanine levels), treatment and treatment guidelines.

    Cognitive and internalizing behavioural problems were mainly observed in adult PKU patients. Among adolescents with PKU, problems with social cognition were also observed, but generally such difficulties were most pronounced in adult patients. Problems in all domains were related to high phenylalanine levels at different stages in life.

    There are several important findings concerning treatment guidelines. Patients with phenylalanine concentrations below 360 µmol/L in childhood and above 360 µmol/L from adolescence onwards had better cognitive outcome in adulthood than those with phenylalanine above 360 µmol/L during their lifespan. Childhood phenylalanine seemed most important for cognitive and mental health outcomes in adulthood. A greater increase of phenylalanine between childhood and adolescence also seemed important for cognitive outcome in adulthood. Moreover, a phenylalanine level of 240 µmol/L may be a better treatment target in childhood for better cognitive functioning compared to the most widely recommended upper target phenylalanine limit of 360 µmol/L.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • van Spronsen, Francjan, Supervisor
    • van der Meere, Jaap, Supervisor
    • Huijbregts, S. C. J., Co-supervisor, External person
    • Lachmann, R H, Assessment committee, External person
    • Smit, Peter, Assessment committee
    • Tucha, Oliver, Assessment committee
    Award date27-Jun-2017
    Place of Publication[Groningen]
    Print ISBNs978-90-367-9903-4
    Electronic ISBNs978-90-367-9902-7
    Publication statusPublished - 2017

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