Blood-brain barrier phenylalanine transport and individual vulnerability in phenylketonuria.

In vivo nuclear magnetic resonance spectroscopy can be used to measure intracerebral phenylalanine (Phe) concentrations in patients with phenylketonuria (PKU). Stationary levels, obtained under free nutrition, as well as time courses after an oral Phe load (100 mg/kg) were investigated in 11 PKU patients and were correlated with the individual clinical outcome. At blood levels around 1.2 mmol/L, brain Phe was 0.41 to 0.73 mmol/L in clinically "typical" patients, but less than 0.15 mmol/L in three untreated, normally intelligent, adult women. Kinetic investigations revealed higher transport Michaelis constants and lower ratios of the brain influx and consumption rates in these women than in the "typical" control patients (Kt,app = 0.45 to 1.10 mmol/L versus 0.10 mmol/L; T(max)/v(met) = 2.55 to 3.19 versus 7.8 to 14.0). Such variations seem to be major causative factors for the individual vulnerability to PKU.