European Journal of Pediatrics

, Volume 159, Supplement 2, pp S109–S113 | Cite as

The neurochemistry of phenylketonuria

  • Robert Surtees
  • Nenad Blau


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 deficiency Hyperphenylalaninaemia Neurotransmitters Demyelination Central nervous system 
AbbreviationsBH4 tetrahydrobiopterin GTP guanosine triphosphate GFRP GTPCH feed-back regulatory protein GTPCH GTP cyclohydrolase I HPA hyperphenylalaninaemia PAH phenylalanine 4-hydroxylase Phe phenylalanine PKU phenylketonuria PTPS 6-pyruvoyltetrahydropterin synthase SR 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

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