Maternal phenylketonuria: Magnetic resonance imaging of the brain in offspring

Phenylketonuria (PKU) produces white matter changes identifiable by magnetic resonance imaging. These changes occur postnatally. Offspring of untreated mothers with PKU also have a brain effect, expressed as microcephaly and mental retardation. This effect occurs prenatally. To determine whether the white matter changes seen in PKU are also present in maternal PKU offspring, despite the different developmental stages of exposure to PKU, we performed brain magnetic resonance imaging studies in seven maternal PKU offspring, five from essentially untreated pregnancies and two from treated pregnancies. None had white matter changes, although the one offspring with PKU had delayed myelination. However, hypoplasia of the corpus callosum was present in three of the four offspring from untreated pregnancies and in the offspring from a maternal PKU pregnancy not treated until the third trimester. Unlike PKU, white matter changes are not a feature of the brain effect in maternal PKU. However, hypoplasia of the corpus callosum is a feature of maternal PKU and is probably a result of inhibition of corpus callosum development at 8 to 20 weeks of gestation. The hypoplastic corpus callosum could be a marker for brain effect in maternal PKU and may have implications for the cognitive deficits in these offspring.