The neurochemistry of phenylketonuria

The mechanisms by which deficiency of hepatic phenylalanine hydroxylase cau ses central nervous system disease are reviewed. The neurological disease a ppears to be secondary to increased concentrations of phenylalanine and a d ecrease in the concentrations of other large neutral amino acids, especiall y 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 phenyl alanine concentrations are in the range expected for early continuously tre ated phenylketonuria. Conclusion The severe brain disease found in phenylketonuria is caused by a raised blood phenylalanine content which increases the brain free phenylal anine and decreases the concentration of other large neutral amino acids. B rain protein synthesis is decreased, myelin turnover is increased and there are abnormalities in amine neurotransmitter systems.