Phenylalanine blood levels and clinical outcomes in phenylketonuria: A systematic literature review and meta-analysis
DOI: 10.1016/j.ymgme.2007.05.006
Title: Phenylalanine blood levels and clinical outcomes in phenylketonuria: A systematic literature review and meta-analysis
Journal Title: Molecular Genetics and Metabolism
Volume: 92
Publication Date: September–October 2007
Start Page: 63
End Page: 70
Published online: online 25 June 2007
ISSN: 1096-7192
Author: Susan E. Waisbrena, Kay Noelb, Kyle Fahrbachb, Catherine Cellab, Diana Frameb, Alex Dorenbaumc, Harvey Levya
Affiliations:

  • a Children’s Hospital Boston, 1 Autumn Street, Room 525, Boston, MA 02115, USA

  • b United BioSource Corporation, 101 Station Landing, Medford, MA 02155, USA

  • c BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA
  • Abstract: trong>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.
    Accepted: 10 May 2007
    Received: 11 April 2007
    Revised: 10 May 2007
    Keywords: Biomarker; Predictive biomarker; Intelligence quotient
    Email: susan.waisbren@childrens.harvard.edu

    Please Share this Paper with friends:
    Comment
    No.
    Comment Content
    User Name
    Date
    Post new Comment
    UserName