title: New evidence for assessing tetrahydrobiopterin (BH(4)) responsiveness.
abstract: OBJECTIVE
  To evaluate the protocol we propose for detecting BH(4)-responsive patients and the possibility of delimiting more precisely the population to be tested.
  
  
  METHODS
  We recruited 102 phenylketonuric patients on a phenylalanine (Phe)-restricted diet. The initial stage of the protocol was a 24-h BH(4) loading test involving Phe loading and subsequent ingestion of the cofactor, a 50% fall in blood Phe levels being considered a positive response. The non-responders at this stage then completed a one-week therapeutic test combining BH(4) administration and daily protein intake meeting recommended dietary allowances, to assess whether the 24-h test had detected all responders.
  
  
  RESULTS
  The 24-h test detected almost all BH(4) responders (30.3% of the 99 patients included in the analysis), with just two patients (2.0%) subsequently responding positively to the therapeutic test. The 24-h test did not give any false positive results.
  
  
  CONCLUSIONS
  The 24-h BH(4) loading test is clinically useful for screening phenylketonuric patients. Specifically, 95% of patients with Phe levels <700 μmol/L, and none with Phe levels >1500 μmol/L were BH(4)-responsive. Given these results, we conclude that patients with Phe levels<700 μmol/L or>1500 μmol/L probably do not need to be tested, prioritising the identification of BH(4)-responsiveness among individuals with intermediate Phe concentrations, between the aforementioned values. Additionally, our results suggest that the therapeutic test only needs to be performed in cases where the reduction in blood Phe levels after cofactor administration is within the range 40%-50%.
authors.affiliation: Metabolic Disorders, Dietetics and Nutrition Unit, Virgen del Rocío Teaching Hospital, s/n, 41013, Sevilla, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Bueno
authors.forename: Sergio
authors.initials: S
authors.lastname: Lage
authors.forename: Carmen
authors.initials: C
authors.lastname: Delgado
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
authors.forename: María L
authors.initials: ML
authors.lastname: Couce
authors.forename: Domingo
authors.initials: D
authors.lastname: González-Lamuño
authors.forename: Manuel
authors.initials: M
authors.lastname: Pérez
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D010649:Phenylalanine / Q000008:administration & dosage; D010661:Phenylketonurias / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy*; D010865:Pilot Projects; D015203:Reproducibility of Results; D013030:Spain; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin