title: Testing for tetrahydrobiopterin responsiveness in patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency.
abstract: BACKGROUND
  Pharmacological levels of the phenylalanine hydroxylase enzyme cofactor, tetrahydrobiopterin (BH4), reduce plasma phenylalanine levels in some patients with phenylketonuria (PKU), providing the first pharmacological therapy for PKU. Responsiveness to this therapy must be determined empirically through a BH4 loading test or trial. The authors have analyzed the loading tests currently in use in light of the numerous factors that can influence their results. Sapropterin dihydrochloride is a stable, synthetic form of BH4 approved for treatment of PKU in responsive patients.
  
  
  METHODS
  An expert panel identified evidence from published reports of clinical experience. Reports of research involving at least 25 patients and published in English were considered.
  
  
  RESULTS
  In all, 14 studies met both criteria; eight employing the sapropterin dihydrochloride preparation from Schircks Laboratories and six the sapropterin dihydrochloride preparation from Biomarin/Merck Serono.
  
  
  CONCLUSIONS
  The arbitrary responsiveness definition of a >30% reduction in blood phenylalanine appears to be a good compromise between sensitivity and specificity for the initial screening test. However, individual patient characteristics should be considered when interpreting results, especially in patients with low baseline phenylalanine levels.
authors: Reference Center for Neonatal Screening and Diagnosis for Metabolic Diseases of University-Istituto Giannina Gaslini, Via 5 maggio, 3916147 Genoa, Italy. robertocerone@ospedale-gaslini.ge.it
authors: Roberto
authors: R
authors: Cerone
authors: Generoso
authors: G
authors: Andria
authors: Marcello
authors: M
authors: Giovannini
authors: Vincenzo
authors: V
authors: Leuzzi
authors: Enrica
authors: E
authors: Riva
authors: Alberto
authors: A
authors: Burlina
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D018579:Patient Selection; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000188:drug therapy*
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin