Effect of high-dose tyrosine supplementation on brain function adults with phenylketonuria in Joachim Pietz, MD, Ralf Landwehr, Ansgar Kutscha, MS, Hildgund Schmidt, MD, Leo de Sonneville, PhD, and Friedrich K. Trefz, MD a From the Departments of Pediatric Neurology and General Pediatrics, University of Heidel- berg, Germany, and the Academisch Ziekenhuis Vrje Universiteit Policlinic, Free University of Amsterdam, The Netherlands Objectives: To characterize abnormalities of brain function in patients with phe- nylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect. Design: 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. Subjects: Twenty-four early-treated patients with PKU aged 20.8 (I 6 to 25) years; 24 control subjects. Methods: Plasma concentrations of phenylalanine and Tyr were monitored. Neu- ropsychologic tasks, visual evoked potentials, and spectral analysis of electro- encephalographic 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 sus- tain attention, prolonged latencies of visual evoked potential peaks NI 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. (J PEDIATR 1995; 127:936-43) When given a phenylalanine-restricted diet, children with "classic" phenylketonuria have normal or nearly normal intellectual development,l although IQs tend to be somewhat lower than in healthy siblings.2 Former recommendations to Supported by grants from the German Federal Department of Re- search and Technology (FKZ 706562) and the German Research Foundation (Pi196/3-1) to J. Pietz and by SHS-Gesellschaft f'ttrkli- nische Emahrung mbH. Submitted for publication May 10, 1995; accepted July 24, 1995. Reprint requests: Joachim Pietz, MD, Department of Pediatric Neurology, University of Heidelberg, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany. aNow at Children's Hospital, Reutlingen, Germany. Copyright © 1995 by Mosby-Year Book, Inc. 0022-3476/95/$5.00 + 0 9/20/68053 stop diet therapy during school age or adolescence have been replaced by more or less strict recommendations for a "diet for life." This trend was initiated after new information CSF Cerebrospinal fluid DPE Dot Pattern Exercise [neuropsychologic task] FMSE Finger Motor Speed Exercise [neuropsychologic task] Phe Phenylalanine PKU Phenylketonuria RT Reaction time Tyr Tyrosine VEP Visual evoked potential showed a decrease in IQ when diet was stopped in early school age, 3 the occurrence of late-onset neurologic symp- toms years after dietary treatment was ended, 4 frequent ob- 936