European Journal of Pediatrics

, Volume 159, Supplement 2, pp S109–S113

The neurochemistry of phenylketonuria

  • Robert Surtees
  • Nenad Blau

DOI: 10.1007/PL00014370

Cite this article as:
Surtees, R. & Blau, N. Eur J Pediatr (2000) 159: S109. doi:10.1007/PL00014370


The mechanisms by which deficiency of hepatic phenylalanine hydroxylase causes central nervous system disease are reviewed. The neurological disease appears to be secondary to increased concentrations of phenylalanine and a decrease in the concentrations of other large neutral amino acids, especially methionine and tyrosine, within the central nervous system. This causes a deficiency of the neurotransmitter dopamine, reduced protein synthesis and demyelination. Similar mechanisms appear to be operating when blood phenylalanine concentrations are in the range expected for early continuously treated phenylketonuria.

Conclusion The severe brain disease found in phenylketonuria is caused by a raised blood phenylalanine content which increases the brain free phenylalanine and decreases the concentration of other large neutral amino acids. Brain protein synthesis is decreased, myelin turnover is increased and there are abnormalities in amine neurotransmitter systems.

Key words Phenylalanine hydroxylase deficiencyHyperphenylalaninaemiaNeurotransmittersDemyelinationCentral nervous system
AbbreviationsBH4 tetrahydrobiopterinGTP guanosine triphosphateGFRP GTPCH feed-back regulatory proteinGTPCH GTP cyclohydrolase IHPA hyperphenylalaninaemiaPAH phenylalanine 4-hydroxylasePhe phenylalaninePKU phenylketonuriaPTPS 6-pyruvoyltetrahydropterin synthaseSR sepiapterin reductase

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Robert Surtees
    • 1
  • Nenad Blau
    • 2
  1. 1.Institute of Child Health (UCLMS), 30, Guilford Street, London WC1N 1EH, UK e-mail: Tel.: +44-20-7837-7618; Fax: +44-20-7833-7618GB
  2. 2.University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, SwitzerlandCH