Lessening PKU's Damaging Effects on Children

Much of the neurological havoc wreaked by the rare genetic disorder phenylketonuria (PKU) can be prevented through early, thorough, and continuous care.

Findings

Human bodies normally break down proteins like chicken and cheese into amino acids, add enzymes to these amino acids, and then use the good stuff that results for functioning, growth, and repair. Newborns with the rare genetic disorder phenylketonuria (PKU), however, have little or none of the enzyme that turns the amino acid phenylalanine (Phe) into the good stuff known as tyrosine. In the absence of this enzyme (called phenylalanine hydroxylase enzyme), Phe builds up in the newborns' blood, poisons their brain tissues, and causes mental retardation and other neurological deficits, including problems with working memory and impulse control. At the same time, tyrosine levels languish.

PKU's damage can be lessened by putting newborns on a Phe-restriced diet, which lowers their blood Phe levels. Indeed, some studies show no differences in the IQ's of children without PKU and children whose PKU has been consistently and carefully controlled through diet. But how low should blood Phe be? And how early must children start the Phe-restriced diet to prevent PKU's harmful effects? When developmental cognitive neuroscientist Adele Diamond began her research, experts thought that levels lower than 10 milligrams of Phe per deciliter of blood (10 mg/dl) were safe. Yet Dr. Diamond's studies showed that children with blood Phe levels greater than 6 mg/dl suffered significant cognitive deficits, while children with blood Phe level less than 6 mg/dl did not. Dr. Diamond also showed that if newborns are not given a Phe-restricted diet almost immediately after birth, their deficits are greater and longer-lasting.

Significance

Dr. Diamond's studies show that much of the neurological havoc wreaked by PKU can be prevented by early, thorough, and continuous care. Her studies have also isolated the prefrontal cortex of the brain as the area most affected by the high Phe (and low tyrosine) levels caused by PKU. More broadly, Dr. Diamond's demonstration that diet prevents PKU from lowering intelligence shows that "genetic" does not mean "unchangeable."

Practical Application

Dr. Diamond's research team's findings led the United States and several European countries to lower their target blood Phe levels for children with PKU to 2-6 mg/dL. Their findings also led the U.S. to change its national guidelines so that newborns with PKU are now given a Phe-restricted diet no later than 7-10 days after birth.

Cited Research

Diamond, A. (1994). Phenylalanine levels of 6-10 mg/dl may not be as benign as once thought. Acta Paediatrica, 83 (Supplement 407), 89-91.

Diamond, A., Prevor, M. B., Callender, G.; Druin, D.P. (1997). Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monographs of the Society for Research in Child Development, 62, 1-205.


American Psychological Association, July 8, 2003