Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence

The National Institute of Health (NIH) published a Consensus Statement on the screening and management of Phenylketonuria (PKU) in 2000. The panel involved in the development of this consensus statement acknowledged the lack of data regarding the potential for more subtle suboptimal outcomes and the need for further research into treatment options. In subsequent years, the approval of new treatment options for PKU and outcome data for patients treated from the newborn period by dietary therapy alone have become available. We hypothesized that a review of the PKU literature since 2000 would provide further evidence related to neurocognitive, psychosocial, and physical outcomes that could serve as a basis for reassessment of the 2000 NIH Consensus Statement.

A systematic review of literature residing in PubMed, Scopus and PsychInfo was performed in order to assess the outcome data over the last decade in diet-alone early-treated PKU patients to assess the need for new recommendations and validity of older recommendations in light of new evidence.

The majority of publications (140/150) that contained primary outcome data presented at least one suboptimal outcome compared to control groups or standardized norms/reference values in at least one of the following areas: neurocognitive/psychosocial (N=60; 58 reporting suboptimal outcomes); quality of life (N=6; 4 reporting suboptimal outcomes); brain pathology (N=32; 30 reporting suboptimal outcomes); growth/nutrition (N=34; 29 reporting suboptimal outcomes); bone pathology (N=9; 9 reporting suboptimal outcomes); and/or maternal PKU (N=19; 19 reporting suboptimal outcomes).

Despite the remarkable success of public health programs that have instituted newborn screening and early introduction of dietary therapy for PKU, there is a growing body of evidence that suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology and maternal PKU outcomes are suboptimal. The time may be right for revisiting the 2000 NIH Consensus Statement in order to address a number of important issues related to PKU management, including treatment advancements for metabolic control in PKU, blood Phe variability, neurocognitive and psychological assessments, routine screening measures for nutritional biomarkers, and bone pathology.