ABSTRACT
Phenylketonuria (PKU) was discovered by Foiling in Norway in 1934, as an abnormally high concentration of urine phenylpyruvic acid, or phenylketone, inherited from both parents by Mendelian inheritance with a 1/4 chance of occurrence in each offspring(l). Soon afterward, Jervis showed that the abnormality was due to lack of a single enzyme that converted the essential amino acid, phenylalanine, by a simple hydroxylation step, into the amino acid, tyrosine. In 1939, Block described a simple method for removing phenylalanine from a protein digest and suggested this as a basis for a low phenylalanine diet treatment. In 1953, Bickel demonstrated that such a diet produced a dramatic normalization of behavior in a hyperactive young child with PKU(2). During the next 15 years, this dietary method was applied to many young PKU children to prevent further damage to brain development. Successful effects, however, were only obtained in very young infants discovered by a blood phenylalanine test, performed because an older sibling, already severely retarded, had previously been diagnosed as having PKU.
