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 phe nylketonuria (PKU). Stationary levels, obtained under free nutrition, as well as time courses after an oral Phe load (100 mg/kg) were invest igated in 11 PKU patients and were correlated with the individual clin ical 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 mm ol/L in three untreated, normally intelligent, adult women. Kinetic in vestigations revealed higher transport Michaelis constants and lower r atios of the brain influx and consumption rates in these women than in the ''typical'' control patients (K-t,K-app = 0.45 to 1.10 mmol/L ver sus 0.10 mmol/L; T-max/nu(met) = 2.55 to 3.19 versus 7.8 to 14.0), Suc h variations seem to be major causative factors for the individual vul nerability to PKU.