Variability of blood-brain ratios of phenylalanine in typical patients with phenylketonuria.
Blood-brain ratios (BBR) of phenylalanine (Phe) were determined by quantitative in vivo 1H magnetic resonance spectroscopy (1H-MRS) in 17 adult patients with early-treated phenylketonuria who were randomly selected from a sample of 75 adults. Measurements were performed in all patients during steady-state conditions. The BBR showed a unimodal distribution with a mean of 4.0 (range 3.3 to 4.5). Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe, moderate, or mild and for patients on different types of diets. Brain Phe concentrations showed a strong linear correlation with blood Phe values (r = 0.93, P < 0.001). There were no saturation effects for blood Phe values up to 1.8 mmol/L, and a local regression analysis did not confirm increasing BBR for increasing blood Phe values. The intellectual outcome (Wechsler Adult Intelligence Scale) was correlated with long-term dietary control (r = -0.65, P < 0.05), fluctuation of blood Phe values during treatment (r = -0.60, P < 0.05), and concurrent blood and brain Phe concentration. The severity of white matter changes visible on magnetic resonance images (MRI) was increased with high blood and brain Phe concentrations but failed to reach statistical significance. No correlation was found between BBR values, intelligence quotient, and MRI grade. Based on the assumption that BBR show intraindividual stability, the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of "typical" patients with phenylketonuria.
Rupp
A
A
Department of Pediatric Neurology, University Hospital, Heidelberg, Germany.
Kreis
R
R
Zschocke
J
J
Slotboom
J
J
Boesch
C
C
Rating
D
D
Pietz
J
J
D000293:Adolescent; D000328:Adult; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007360:Intelligence; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010649:Phenylalanine / Q000378:metabolism*; D010661:Phenylketonurias / Q000097:blood* / Q000175:diagnosis; D011522:Protons; D012720:Severity of Illness Index
D011522:Protons; D010649:Phenylalanine