Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria.
OBJECTIVE
To characterize abnormalities of brain function in patients with phenylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect.


METHODS
Comparison with a control group; double-blind, placebo-controlled study comprising six test times; crossover treatment groups; oral high-dose Tyr therapy (100 mg/kg body weight per day) or placebo administration for 4 weeks.


METHODS
Twenty-four early-treated patients with PKU aged 20.8 (16 to 25) years; 24 control subjects.


METHODS
Plasma concentrations of phenylalanine and Tyr were monitored. Neuropsychologic tasks, visual evoked potentials, and spectral analysis of electroencephalographic activity were used to evaluate brain function.


RESULTS
When patients with PKU were compared with control subjects, deficits in certain aspects of brain function were confirmed (i.e., a decreased ability to sustain attention, prolonged latencies of visual evoked potential peaks N1 and P2, and a reduced amount of fast-wave activity on the electroencephalogram). Baseline plasma phenylalanine and Tyr concentrations were in the typical range of adult patients with PKU. The plasma Tyr concentration increased approximately 200% during Tyr supplementation, but no beneficial effects were observed.


CONCLUSIONS
High-dose Tyr supplementation cannot be recommended as an "alternative" treatment for patients with PKU after relaxation or termination of strict dietary adherence.
Pietz
J
J
Department of Pediatric Neurology, University of Heidelberg, Germany.
Landwehr
R
R
Kutscha
A
A
Schmidt
H
H
de Sonneville
L
L
Trefz
F K
FK
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography; D005074:Evoked Potentials, Visual; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000188:drug therapy* / Q000503:physiopathology*; D010919:Placebos; D011581:Psychological Tests; D011930:Reaction Time; D014443:Tyrosine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use*
D010919:Placebos; D014443:Tyrosine; D010649:Phenylalanine