The role of intelligence in phenylketonuria: A review of research and management

Phenylketonuria (PKU) results in profound intellectual disability in untreated individuals and more subtle cognitive deficits in individuals treated early and continuously. The assessment of intellectual functioning has been an important outcome variable and the focus of extensive research. Since the implementation of neonatal PKU screening programs in the 1960s, research on intellectual functioning in individuals with PKU has played a significant and positive role in guiding therapy and improving results. This is a literature review examining the relationship between intellectual outcome and treatment parameters including initiation of treatment, duration of treatment, and blood phenylalanine (Phe) levels from infancy through adulthood. While current PKU treatment practices have eliminated severe neurological and cognitive impairment, evidence suggests that intellectual functioning, although typically within the average range when PKU is treated early and continuously, may not be maximized under the current definition of well-controlled PKU, which is based on blood Phe levels. Future research assessing intellectual and neurocognitive outcome in PKU will enhance the development of new treatment strategies.