CLINICAL CASES
349
Phenylketonuria: The presence of elevated amounts of phenylketones, prima-
rily phenylpyruvate, in urine; a primary indication of disturbance of
phenylalanine metabolism resulting from elevated transamination of
phenylalanine due to reduction in phenylalanine hydroxylation to tyrosine.
D ISC U SSIO N
Phenylketonuria is a disease readily diagnosable in childhood and it is impor-
tant for an optimal clinical outcome for it to be diagnosed as early as possible.
Laboratory tests can be performed in the neonatal period and now genetic test-
ing can identify the trait before birth.
Phenylketonuria obtains from an elevated level of phenylpyruvate in the
urine of the patient. As shown in Figure 38-1, phenylpyruvate is the cognate
a-ketoacid of the amino acid phenylalanine. It is formed by transaminating
phenylalanine and a-ketoglutarate to yield glutamate and phenylpyruvate.
This reaction is freely reversible and therefore driven by elevated concentra-
tions of reactants or products. For large scale conversion of phenylalanine to
phenylpyruvate an increase in the concentration of phenylalanine must occur
to drive the transamination reaction toward the formation of phenylpyruvate.
Such an elevated phenylalanine level will be reflected in the blood as hyper-
phenylalaninemia, which is defined as a plasma phenylalanine level greater
than 120 |jmol/L. The most likely cause is a disturbance in the phenylalanine
hydroxylase reaction. Disease states resulting from disturbances of the pheny-
lalanine hydroxylase reaction can be found (
1
) at the level of the enzymes in
the reaction reflected in absent or altered proteins, (
2
) at the metabolic level
reflected in cognate effects on other metabolic processes, and (3) at the cogni-
tive level reflected in changes in brain function and mental retardation.
Figure 38-1. Transamination of phenylalanine to yield phenylpyruvate, a
phenylketone.
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