Abnormalities of magnetic resonance imaging (MRI) of the brain occur i
n some patients with phenylketonuria but the clinical importance of th
is finding is not clear. In order to determine the frequency and funct
ional significance of changes on MRI we investigated 77 adolescent and
adult patients with phenylketonuria. Patients aged 14-49 years and ta
king a restricted diet of 1 g/kg protein underwent clinical examinatio
n, IQ testing, neurophysiological investigation, and MRI of the brain.
Patients aged between 10-14 years taking a low phenylalanine diet wit
h aminoacid supplements had MRI of the brain only. Biochemical control
was assessed from: the lifetime blood phenylalanine determined from t
he mean blood concentration throughout life; the accumulated time for
each patient that phenylalanine was < 120 mu mol/L; the accumulated ti
me for each patient that phenylalanine was > 1200 mu mol/L); mean bloo
d concentration in the first 4 years of life; and the mean blood phe c
oncentration in the 5 years prior to imaging. MRI changes, compatible
with a disturbance in the water content of white matter, were present
in all but 1 patient. The severity of abnormality was most strongly as
sociated with the blood phenylalanine concentration at the time of ima
ging. Clinical and neurophysiological abnormalities were less common a
nd usually mild. 3 patients had prolonged central motor conduction tim
e, 7 had prolonged visual evoked potentials, and 5 had impaired periph
eral sensory nerve conduction. There was no significant association be
tween the extent of MRI abnormalities and IQ, and the presence of neur
ophysiological, or clinical abnormalities. An abnormal brain scan in P
KU may reflect present biochemical control rather than indicate signif
icant neurological damage. As yet there is little evidence that in mos
t patients with PKU these MRI changes are of clinical importance.