Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis.
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.
Waisbren
Susan E
SE
Children's Hospital Boston, 1 Autumn Street, Room 525, Boston, MA 02115, USA. susan.waisbren@childrens.harvard.edu
Noel
Kay
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Fahrbach
Kyle
K
Cella
Catherine
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Frame
Diana
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Dorenbaum
Alex
A
Levy
Harvey
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D006801:Humans; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood*
D010649:Phenylalanine