Executive and social functioning in early- and continuously-treated patients with PKU: A follow-up study 10 years later

PKU patients are generally on a phenylalanine(Phe)-restricted diet (which
prevents mental and neurological retardation) and receive amino acid
supplements until early adolescence. After this period, the diet is generally
relaxed, resulting in higher Phe levels. As cognitive functioning continues to
develop until at least late adolescence/early adulthood, and societal demands
(whether social, academic, or work-related) increase during this life phase, it
is the question whether relaxation of the diet is harmful or not. Particularly
since the mechanisms through which elevated Phe levels affect the brain (i.e.,
by damaging white matter and by causing dopamine depletion) are in effect
throughout life. Moreover, in early- and continuously-treated PKU, an executive
function (EF) deficit has consistently been found. It is however the question
whether such a deficit extends to other domains of functioning, also for the
younger patients who are still on diet. A question related to both topics
mentioned above is whether current treatment guidelines for different age
groups should be adjusted in light of the cognitive and social demands in daily
life.

The main objective of this study is to examine the executive, social-cognitive,
and social functioning and behaviour of 7-30 year old PKU patients in relation
to history of treatment and treatment adherence. It is expected that there will
be significant differences between PKU patients and controls in executive,
social-cognitive, and social functioning and behaviour. High Phe concentrations
are expected to be related to impairments in these domains. More pronounced
differences are expected in the complex executive functions. The second
objective is to examine the abovementioned constructs in relation to daily life
functioning of PKU-patients (e.g. well-being, quality of life, socio-economic
status, friendships and relations).

Observational longitudinal within- and between-subjects control group design
and cross-sectional control group design. PKU patients, who are now young
adults, and who underwent neuropsychological assessment approximately 10 years
ago are retested, taking into account probable diet relaxation in the last
decade, as well as their level of neuropsychological functioning and treatment
history at the first assessment. A new group of PKU patients will also be
tested with a wider range of instruments (including not only executive
functioning, but also social-cognitive and social functioning and behaviour)
and more refined indicators of dietary control.

Historical phenylalanine concentrations are collected from the data bases of
the clinical centres. Blood samples fall under normal clinical visits and
routine control and do not have to be taken more often than the PKU patients
already have to. Executive functions and social cognition are examined by means
of computerized tasks which will take a maximum of 2.5 hours. Questionnaires
have to be filled out to determine executive and social functioning and
behaviour in daily life. No physical and physiological discomfort is expected,
and no risks are associated with participation in the tasks. The results of the
study may help further determine treatment targets in PKU, but the study may
also help patients and their environment (partner, work, school) to accept (the
consequences of) the disease.