1 Department of Pediatrics, Joseph P. Kennedy Jr. Laboratory, University of Wisconsin Medical Center, Madison, Wisconsin
BESSMAN has raised a number of questions regarding treatment of patients with phenylketonuria (PKU), some of which can be answered by data presently available. The most important of these concerns the expected outcome for an untreated phenylketonuric child. If it is possible, as Bessman suggests, that PKU is often very benign and that we have identified only the atypical severe cases, then the apparent results of treatment may be due simply to observing the more usual course of the disease. Therefore, it is important to study a high-risk group of children who have not previously been tested for PKU. This group consists of those siblings who were already born at the time that the proband was diagnosed. Since routine testing for PKU has only been done recently, these children presumably have not been tested previously.
The number of PKU siblings expected in this group of previously untested brothers and sisters is partially dependent upon the frequency and degree of mental retardation in the disease as suggested by the following possibilities:
1. If mental retardation is incidental in PKU, then one fourth of these siblings would be expected to have PKU as determined by blood and urine tests, and their mental abilities, which might be normal, would be considered typical of untreated phenylketonuric individuals. This would also indicate that most families with PKU members have not been found during the past 10 years, when most cases were ascertained because of mental retardation.
2.If PKU causes severe retardation and urine and blood tests are done on all retarded children, then the first affected child would be identified as the proband in each family; all siblings born before the proband would be non-PKU, and all children with true PKU would be clearly identified.
Submitted on January 17, 1967