Improved Measurement of Brain Phenylalanine and Tyrosine Related to Neuropsychological Functioning in Phenylketonuria.

INTRODUCTION: Researchers hypothesized that in phenylketonuria (PKU) high brain phenylalanine (Phe) levels and low brain tyrosine (Tyr) levels affect neuropsychological functioning. However, traditional magnetic resonance spectroscopy (MRS) yielded uncertain results of brain Phe and could not adequately measure brain Tyr. This pilot study examined the potential of correlated spectroscopy (COSY) to quantify these biomarkers and explain variability in neuropsychological functioning.

METHODS: Nine adults with early treated classic PKU received magnetic resonance imaging (MRI) with COSY and a battery of neuropsychological tests. Brain Phe and Tyr in parietal white matter (PWM) were compared to results in gray matter of the posterior cingulate gyrus (PCG).

RESULTS: Brain Phe ranged from 101 to 182 (mean = 136.76 ± 23.77) μmol/L in PCG and 76 to 185 (mean = 130.11 ± 37.88) μmol/L in PWM. Brain Tyr ranged from 4.0 to 7.4 (mean = 5.44 ± 1.01) μmol/L in PCG and 4.1 to 8.4 (mean = 5.90 ± 1.48) μmol/L in PWM. Correlation coefficients were largest for brain Phe PWM and measures of auditory memory (rho = -0.79), anxiety (rho = 0.79), and executive functioning (rho = 0.69). Associations were in the expected direction, with higher brain Phe and lower brain Tyr related to poorer functioning. The two participants with severe structural MRI abnormalities had low brain Tyr levels in PCG and 3/5 of the participants with moderate to severe MRI abnormalities had higher than average brain Phe levels.

CONCLUSION: COSY has the potential to quantify brain Phe and Tyr at low concentrations and in specific brain regions. In this pilot study, these biomarkers were associated with indices of neuropsychological functioning. Additional studies are needed to validate the COSY results.