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 (Phe) concentrations were quite different in spite of similar blood Phe levels. Interindividual variations of the apparent transport Michaelis constant, Kt,app, covered a range from 0.10 to 1.03mmol/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 Phe levels correlated significantly with the degree of cerebral white matter abnormalities on magnetic resonance images. Correlations of Kt,app, Tmax/Vmet, and the preload brain Phe levels with patients' intelligence scores approached significance. In conclusion, blood–brain barrier Phe transport characteristics and the resultant brain Phe levels seem to be causative factors for the individual clinical outcome in phenylketonuria. This observation may lead to individual dietary recommendations in the future.