Maternal phenylketonuria and hyperphenylalaninemia: Implications for medical practice in the United States

The risk of maternal phenylketonuria and hyperphenylalaninemia syndrome, a preventable cause of severe birth defects and retardation with a near 100% recurrence risk if untreated, is increasing in the United States. The reasons for this are reviewed. Women with hyperphenylalaninemia and those with phenylketonuria diagnosed and treated at birth are intellectually normal, as are some women with undiagnosed phenylketonuria. Both groups are at risk for maternal phenylketonuria syndrome in their offspring if blood phenylalanine levels are not controlled by diet during pregnancy. The problems and pitfalls of suspecting, diagnosing, and managing the condition are discussed. Suggested strategies for reversing the increasing trend include the greater use of genetic registers, increased clinical awareness, and some form of rescreening. The advantages and costs of rescreening a subset of pregnant women or all pregnant women at or before their first registration are examined.