Reply to SP Bessman

Bessman’s historical perspective in this issue (1) provides us with an interesting summary of one side of a controversy that occurred > 20 y ago concerning a possible role for tyrosine in the mental defect of phenylketonuria (PKU) and maternal PKU. Unfortunately, his editorial confuses the difference between early-treated and late-treated PKU. The study by Hsia et al (2) was conducted in institutionalized mentally retarded children and adults who had never received treatment for PKU. It was already known at that time, and we certainly know today, that dietary therapy in such individuals does not raise their intelligence quotient. The real benefit of dietary therapy is in preventing, not reversing, mental retardation by initiating the diet in early infancy. Hardly anyone today would dispute this. Bessman’s editorial contains misleading information about maternal PKU. The unreferenced statement, “Control of maternal phenylalanine concentrations with standard low-phenylalanine regimens did not prevent mental damage to the fetus...”, is inaccurate. From the inception of dietary treatment for maternal PKU it was clear that mental retardation in the offspring could be prevented if the maternal blood phenylalanine concentration was well controlled through diet from either before conception or from early in pregnancy. Current data from the Maternal PKU Collaborative Study strongly support this concept (3). The experimental data from pregnant rats cited in Bessman’s editorial is irrelevant to maternal PKU. The diet for maternal PKU (and for PKU) is phenylalanine deficient, not devoid of phenylalanine. A diet without phenylalanine, which is an essential amino acid, would produce severe depletion and a catabolic state and should never be given for the treatment of PKU. To my knowledge, such a diet is never prescribed. Finally, although tyrosine supplementation might be helpful in the treatment of PKU, treatment of PKU with tyrosine alone without a low-phenylalanine diet would be disastrous and would result in severe mental retardation. Bessman himself pointed this out more than a decade ago (4).