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Age-related psychophysiological vulnerability to phenylalanine in phenylketonuria.
[phenylketonuria]
Phenylketonuria
(
PKU
)
is
caused
by
the
inherited
defect
of
the
phenylalanine
hydroxylase
enzyme
,
which
converts
phenylalanine
(
Phe
)
into
tyrosine
(
Tyr
)
.
Neonatal
screening
programs
and
early
treatment
have
radically
changed
the
natural
history
of
PKU
.
Nevertheless
,
an
increased
risk
of
neurocognitive
and
psychiatric
problems
in
adulthood
remains
a
challenging
aspect
of
the
disease
.
In
order
to
assess
the
vulnerability
of
complex
skills
to
Phe
,
we
explored
:
(
a
)
the
effect
of
a
rapid
increase
in
blood
Phe
levels
on
event-related
potentials
(
ERP
)
in
PKU
subjects
during
their
second
decade
of
life
;
(
b
)
the
association
(
if
existing
)
between
psychophysiological
and
neurocognitive
features
.
Seventeen
early
-treated
PKU
subjects
,
aged
10
-
20
,
underwent
ERP
[
mismatch
negativity
,
auditory
P
300
,
contingent
negative
variation
(
CNV
)
,
and
Intensity
Dependence
of
Auditory
Evoked
Potentials
]
recording
before
and
2
 
h
after
an
oral
loading
of
Phe
.
Neurocognitive
functioning
,
historical
and
concurrent
biochemical
values
of
blood
Phe
,
Tyr
,
and
Phe
/
Tyr
ratio
,
were
all
included
in
the
statistical
analysis
.
Event-related
potential
components
were
normally
detected
in
all
the
subjects
.
In
subjects
younger
than
13
CNV
amplitude
,
W
2
-
CNV
area
,
P
3
b
latency
,
and
reaction
times
in
motor
responses
were
negatively
influenced
by
Phe-loading
.
Independently
from
the
psychophysiological
vulnerability
,
some
neurocognitive
skills
were
more
impaired
in
younger
patients
.
No
correlation
was
found
between
biochemical
alterations
and
neurocognitive
and
psychophysiological
findings
.
The
vulnerability
of
the
emerging
neurocognitive
functions
to
Phe
suggests
a
strict
metabolic
control
in
adolescents
affected
by
PKU
and
a
neurodevelopmental
approach
in
the
study
of
neurocognitive
outcome
in
PKU
.
Diseases
Validation
Diseases presenting
"oral loading"
symptom
classical phenylketonuria
phenylketonuria
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