Evaluation of Behavior, Cognition, and Electroencephalograms in PKU Heterozygotes

Aspartame (L-aspartyl-L-phenylalanine methyl ester) is metabolized by enzymes in the gastrointestinal tract to the two amino acids - aspartic acid and phenylalanine - and methanol. The phenylalanine component has received special consideration due to its connection to phenylketonuria (PKU). PKU is an autosomal-recessive inherited disease which, when present in the homozygous form, is expressed in its known clinical form of microcephaly, mental retardation, and other abnormalities. It affects approximately 1:15,000 newborns each year in countries such as the U.S. and Germany; however, the prevalence varies around the world from about 1:4500 in Ireland to about 1:100,000 in Finland. The disease is characterized by an inborn error in the production of the liver enzyme, phenylalanine hydroxylase, that is responsible for the metabolism of the essential amino acid, phenylalanine, to tyrosine. Through newborn screening programs in many countries, PKU individuals are identified at birth and treated with special low phenylalanine diets from shortly after birth to prevent the damages described above. Early identification and adequate treatment result in normal health with normal intellectual development. If untreated, plasma phenylalanine concentrations in PKU may be as much as 20 to 50 times normal, and the situation usually leads to progressive brain dysfunction with mental retardation and often seizures.