Maternal Phenylketonuria: Experiences From the United Kingdom

Abstract

Charles Dent was one of the first physicians to recognize the teratogenic effects of maternal phenylalanine (Phe) on the fetus in 1956. This article describes the clinical experiences of women with phenylketonuria (PKU) within the unit that was established by Dent in the United Kingdom. Between 1977 and 2002, 79 infants were born to women with PKU. Of the 79, 18 (23%) were conceived while the women were on a normal diet with high blood Phe levels. The mean birth weight was 2.89 kg, and head circumference was 32.8 cm. At 1 year, the mean developmental quotient was 105.5 and at 4 years was 82.3. Four of these infants had congenital heart disease (2 of whom died as a result). In the remaining 61 infants, Phe-restricted diet started before conception. None of them had congenital heart disease. The mean birth weight was 3.23 kg, and head circumference was 34.0 cm. At 1 year, mean developmental quotient was 108.0 and at 4 years was 90.9. They continue to be followed up with additional neuropsychometric assessments at 8 and 14 years of age. This cohort is a proportion of infants who were born to mothers with PKU in the United Kingdom. Between 1978 and 1997, 255 live births were reported. Of these, 56% were conceived on unrestricted diet with subsequently poor outcome. This relatively high rate of conception off PKU diet is likely to reflect the scarcity of medical services for adults with metabolic disorders. We conclude that many features of the maternal PKU syndrome can be prevented but still occur because of the lack of appropriate resources to care for at-risk women. The precise targets for blood Phe and other nutrients during pregnancy are not entirely clear, neither are the reasons that some offspring are spared the harmful effects of Phe. The impact of the postnatal environment in which these infants find themselves requires additional assessment, too.