An occipito‐temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia

Abstract

The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200-300 mumol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 mumol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.

White matter abnormalities in patients with treated hyperphenylalaninaemia: Magnetic resonance relaxometry and proton spectroscopy findings

“…In all patients, spectra were obtained at TE = 270 ms to optimize lactate detection [21], however in none a definite lactate peak was found. Our findings correspond well with results recently published by Lou et al [35], who also found normal proton spectra in two patients with HPA. Johannik et al [28] observed a reduction in relative inositol concentration in PKU patients using a shorter echo time (TE = 20 ms).…”

“…Regression of MRI abnormalities after reinstitution of strict diet treatment has also been reported by two other groups [5,52]. Our data as well as the data from the literature indicate, that a significant regression of MRI white matter abnormalities under diet may only be expected with plasma Phe levels below 0.36 mmol/l [35]. This range of Phe values corresponds well to plasma Phe concentrations which are considered safe during early childhood [50].…”

“…Since the first description in 1989 [8,56], more than 180 patients with similar findings have been reported in the literature [5,9,11,14,34,35,41,42,48,49,[52][53][54]58]. A summary of MR and CT findings in patients with HPA is presented in Table 1.…”

“…Although these findings may be demonstrated in the majority of classical PKU patients, a large degree of interindividual variation exists regarding the extent of MRI abnormalities. In general, changes are less pronounced in patients with good dietary control at the time of MR examination [34,35,48,53,54].…”

Visual event‐related potentials in children with phenylketonuria

“…Recent advances in brain imaging have also shown abnormalities in patients with PKU. Magnetic resonance imaging (MRI) has shown abnormalities in the white matter of the brain in asymptomatic, early-treated children and adults (6,7). These MRI abnormalities were related to recent levels of Phe and length of time since dietary treatment ceased, and were independent of Phe levels early in life (6).…”