Maternal Phenylketonuria

Abstract

Prior to newborn screening and the availability of dietary treatment for phenylketonuria, most patients with classic phenylketonuria developed profound mental retardation and rarely reproduced.1,2 Newborn screening for phenylketonuria has been routinely available throughout the United States for approximately 25 years. Many infants who were identified as having elevated blood phenylalanine concentrations received dietary treatment. In most cases they have attained normal intelligence. A significant number of women who are no longer being treated have entered or are approaching their reproductive years. When diet is discontinued, elevated blood phenylalanine concentrations and other biochemical changes of classic phenylketonuria again become evident. Children born to mothers whose blood phenylalanine concentrations exceed 0.6 mM (10 mg/dL) have an extremely high incidence of microcephaly and mental subnormality due to the teratogenic effects of phenylalanine and its metabolites.1-8 The incidence of other congenital anomalies, such as congenital heart defects, is also increased. When blood phenylalanine concentrations are less than 0.6 mM(10 mg/dL), the effect on offspring appears to be less severe and less constant. The outcome of such pregnancies is being investigated in a collaborative study sponsored by the National Institutes of Health.1,7 Additional data will become available soon. All women with persistent phenylalanine elevations should be counseled prior to pregnancy about the possible adverse effect of their condition on their offspring. These women should also be counseled about the risk that their child might have phenylketonuria (approximately 1/120). Reproductive options should be discussed. Women who decide to proceed with pregnancy should be advised that dietary treatment may improve the outcome for their child.2-4,7-9