Phenylalanine blood levels and clinical outcomes in phenylketonuria: A systematic literature review and meta-analysis

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• 作者：Susan E. Waisbren ; Kay Noel ; Kyle Fahrbach ; Catherine Cella ; Diana Frame ; Alex Dorenbaum ; Harvey Levy
• 关键词：Biomarker ; Predictive biomarker ; Intelligence quotient
• 刊名：Molecular Genetics and Metabolism
• 出版年：2007
• 出版时间：September-October 2007
• 年：2007
• 卷：92
• 期：1-2
• 页码：63-70
• 全文大小：168 K

文摘

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 μmol/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 μmol/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.