title: Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis.
abstract: Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r=-0.35; 95% confidence interval [CI]: -0.44 to -0.27), where each 100 micromol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r=0.34; 95% CI: -0.42 to -0.25), where each 100 micromol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.
authors.affiliation: Children's Hospital Boston, 1 Autumn Street, Room 525, Boston, MA 02115, USA. susan.waisbren@childrens.harvard.edu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waisbren
authors.forename: Kay
authors.initials: K
authors.lastname: Noel
authors.forename: Kyle
authors.initials: K
authors.lastname: Fahrbach
authors.forename: Catherine
authors.initials: C
authors.lastname: Cella
authors.forename: Diana
authors.initials: D
authors.lastname: Frame
authors.forename: Alex
authors.initials: A
authors.lastname: Dorenbaum
authors.forename: Harvey
authors.initials: H
authors.lastname: Levy
mesh_terms: D006801:Humans; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood*
chemical_list: D010649:Phenylalanine