Comparison of treated and untreated pregnancies in a mother with phenylketonuria

We have studied a family in which the mother has PKU and has had six pregnancies, three untreated and three treated with a low-phenylalanine diet begun during the first or second trimester. The three nonphenylketonuric offspring from two of the untreated pregnancies are mentally retarded and microcephalic. The two nonphenylketonuric offspring from two of the treated pregnancies are also microcephalic and have low or borderline low intelligence. One untreated pregnancy resulted in spontaneous abortion. One treated pregnancy resulted in stillbirth at seven months. It is not certain that dietary treatment of maternal PKU during pregnancy, when begun after conception, is sufficient to protect the fetus. This therapy may have to be ongoing at the time of conception for optimal fetal protection.