ALTHOUGH the genetic defect in the hereditary disorder phenylketonuria has been related to the lack of one of the enzymes involved in the hydroxylation of phenylalanine, the cause of the mental retardation remains unknown.
Bickel et al.1 and other workers noted dramatic improvement in intelligence and developmental quotients of certain phenylketonuric children who were fed diets low in phenylalanine content. Concomitantly, the blood phenylalanine levels of these children fell to within the range found in normal children. Hence, the mental retardation has been attributed to some metabolic disorder associated with elevated blood and tissue levels of phenylalanine.
Armstrong et al.2 found that phenylketonurics excrete more of certain tryptophan metabolites, such as indoleacetic acid, than do normal children, and Pare et al.3 later showed that the blood levels of 5-hydroxytryptamine (serotonin) were lower, and the urinary excretion of 5-hydroxyindoleacetic acid was less, in phenylketonurics than in other mentally
Reichle FA, Baldridge RC, Dobbs J, Trompetter M. Tryptophan Metabolism in Phenylketonurics. JAMA. 1961;178(9):939–941. doi:10.1001/jama.1961.73040480023018