Apparent Absence of Amines in Cerebrospinal Fluid of Phenylketonurics

Abstract

THE mechanism by which mental defect is produced in phenylketonuria is unknown. No correlation has been found in patients having this disorder between the degree of mental defect and blood-levels of phenylalanine or phenylpyruvate, or urinary excretion of phenylalanine, phenyllactate, phenylpyruvate or o-hydroxyphenylacetate¹. The possible implication of biologically active amines has been examined in several papers. Mitoma et al. ² administered o-tyrosine and m-tyrosine to experimental animals and observed conversion to the corresponding amines in brain, with attendant central nervous system stimulation and convulsions. Association of the mental defect in phenylketonuria with an excessive production of o-tyramine was suggested. It also seems possible that overproduction of phenylethylamine may be responsible for the disturbance in cerebral metabolism. Jepson et al. ³ have recently shown that administration of a monoamine oxidase inhibitor to phenylketonuric individuals results in an increase much greater than normal in the urinary excretion of phenylethylamine, but not of o-tyramine. The mental defect in phenylketonuria may also be due to an underproduction of amines vital to normal brain function. Pare et al. ⁴ have reported low serum serotonin-levels and decreased urinary excretion of 5-hydroxyindoleacetic acid in phenylketonuria. They suggest that one or more aromatic acid metabolites of phenylalanine inhibit 5-hydroxytryptophan de-carboxylase, the enzyme responsible for the production of serotonin.