Individual blood-brain barrier phenylalanine transport determines clinical outcome in phenylketonuria.

Different clinical outcomes in spite of comparable dietary controls are well known in patients with phenylketonuria. Currently, reasons for this phenomenon are unknown. Kinetic investigations in 15 patients with classic phenylketonuria were performed using in vivo nuclear magnetic resonance spectroscopy before and after an oral phenylalanine load (100 mg/kg body weight). Patients' brain phenylalanine concentrations were quite different in spite of similar blood phenylalanine levels. Interindividual variations of the apparent transport Michaelis constant, K(t,app), covered a range from 0.10 to 1.03 mmol/L. The ratio of the maximal transport velocity, Tmax, over the intracerebral consumption rate, Vmet, varied between 2.61 and 14.0. Both parameters as well as the preload brain phenylalanine levels correlated significantly with the degree of cerebral white matter abnormalities on magnetic resonance images. Correlations of K(t,app), Tmax/Vmet, and the preload brain phenylalanine levels with patients' intelligence scores approached significance. In conclusion, blood-brain barrier phenylalanine transport characteristics and the resultant brain phenylalanine levels seem to be causative factors for the individual clinical outcome in phenylketonuria. This observation may lead to individual dietary recommendations in the future.