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Phenylketonuria is a human model for the study of the effects of phenylalanine on brain function. We found previously a correlation between high blood phenylalanine, prolonged performance times on neuropsychological tests of higher integrative function, and decreased urinary dopamine in 10 patients. In this protocol we examine changes in triplicate of plasma dihydroxyphenylalanine (L-DOPA) and the mean power frequency of the electroencephalogram in eight additional older patients with phenylketonuria using longer intervals in a blinded, cross-over design. Mean power frequency was obtained by Fourier transform of the power spectrum from traditional eight channel electroencephalograms. Plasma L-DOPA was quantitated by radioenzymatic methods. In all patients statistically significant decreases were found in the mean power frequency of the electroencephalogram and in plasma L-DOPA when plasma L-phenylalanine increased. These findings were reversible and correlated in the reverse direction when plasma L-phenylalanine was reduced. Thus changes in the mean power frequency of electroencephalograms and circulating L-DOPA offer sensitive parameters of human brain function in vivo. These findings indicate reversible effects of elevated plasma phenylalanine on electrical function of the brain which may be mediated in part through inhibition of catecholamine synthesis.

Phenylalanine Alters the Mean Power Frequency of Electroencephalograms and Plasma L-DOPA in Treated Patients with Phenylketonuria