Conference on treatment of phenylketonuria

Abstract

Summary Two major problems were repeatedly emphasized throughout this conference: (1) the uncertainty of diagnosis, and (2) the need for evaluation of dietary therapy. To a great extent the evaluation of therapy is dependent upon a correct diagnosis. The following recommendations are centered about these two points. Recommendations Diagnosis. There is great need for an improvedclinical, genetic, biochemical, and possibly psychological definition of “phenylalaninemia.” Though present methodology in these areas may be somewhat less than desirable, nevertheless its consistent and appropriate use and interpretation would undoubtedly clarify a number of important issues. These would include: measurement of phenylalanine hydroxylase enzyme activity in liver tissue obtained in selected patients by needle biopsy; use of phenylalanine loading tests in parents of infants with “phenylalaninemia”; longitudinal clinical, biochemical, and psychological follow-up of infants with phenylalaninemia who do not have the other typical biochemical manifestations of classical phenylketonuria; definition of treatment in terms of amounts of phenylalanine needed to achieve biochemical control; source of phenylalanine; and duration of treatment. Therapy 1. The assumption is generally made that phenylalanine or one of its metabolites is toxic to the developing brain. As yet there is no evidence to support this statement. Animal studies have been inconclusive. No correlation between the levels of serum phenylalanine or its metabolites and the severity of brain damage has been found. These points deserve careful consideration and emphasize the need for continued basic investigation in this area, since they are fundamental to development of improved therapy of the disease. For the present we can only assume that the increased phenylalanine or its products are toxic to the developing nervous system and that their removal through the diet is beneficial to the patient. 2. The management of patients on the low phenylalanine diet is best carried out by an experienced team of professional personnel at a medical center. In infants suspected of having phenylketonuria, the diagnosis should be confirmed by persons experienced in evaluating this problem. Treatment based on an inadequate or incorrect diagnosis may lead to serious problems for the infant. 3. More attention must be given to psychologic evaluation of the results of dietary therapy. Tests which provide a profile of abilities and disabilities should be used rather than those measuring only IQ. “Normal” or “retarded” must be defined in terms of the function involved. 4. An evaluation should be made of the effects of psychological and psychosocial factors in dietary management, effects on psychologic testing, impact on the family, and the like. Collaborative studies Research involving treatment centers for phenylketonuria should be supported. These studies can establish standards for diagnosis and therapy and evaluation, thus ensuring comparable data from a number of series of patients.