title: The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline phenylalanine concentration.
abstract: BACKGROUND
  The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 μmol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400 μmol/l minimum baseline phenylalanine concentration.
  
  
  METHODS
  Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400 μmol/l. BH4 20mg/kg was administered at T = 0 and T = 24. Blood samples were taken at T=0, 8, 16, 24 and 48 h. Responsiveness was defined as ≥ 30% reduction in phenylalanine concentration at ≥ 1 time point.
  
  
  RESULTS
  Eighty-six (46.2%) patients were responsive. Among responders 84% showed a ≥ 30% response at T = 48. Fifty-three percent had their maximal decrease at T = 48. Fourteen patients had ≥ 30% phenylalanine decrease not before T = 48. A ≥ 30% decrease was also seen in patients with phenylalanine concentrations <400 μmol/l.
  
  
  CONCLUSIONS
  In the 48-hour BLT, T = 48 seems more informative than T = 24. Sampling at T = 32, and T = 40 may have additional value. BH4 responsiveness can also be predicted with baseline blood phenylalanine <400 μmol/l, when the BLT is positive. Therefore, if these results are confirmed by data on long-term BH4 responsiveness, we advise to first perform a BLT without phenylalanine loading and re-test at higher phenylalanine concentrations when no response is seen. Most likely, the 48-hour BLT is a good indicator for BH4 responsiveness, but comparison with long term responsiveness is necessary.
authors: Beatrix Children's Hospital, University Medical Centre Groningen, The Netherlands. anjemak@umcg.nl
authors: K
authors: K
authors: Anjema
authors: G
authors: G
authors: Venema
authors: F C
authors: FC
authors: Hofstede
authors: E C
authors: EC
authors: Carbasius Weber
authors: A M
authors: AM
authors: Bosch
authors: N M
authors: NM
authors: Ter Horst
authors: C E M
authors: CE
authors: Hollak
authors: C F
authors: CF
authors: Jonkers
authors: M E
authors: ME
authors: Rubio-Gozalbo
authors: E M C
authors: EM
authors: van der Ploeg
authors: M C
authors: MC
authors: de Vries
authors: R G
authors: RG
authors: Janssen-Regelink
authors: M C H
authors: MC
authors: Janssen
authors: H
authors: H
authors: Zweers-van Essen
authors: C C A
authors: CC
authors: Boelen
authors: N A P
authors: NA
authors: van der Herberg-van de Wetering
authors: M R
authors: MR
authors: Heiner-Fokkema
authors: M
authors: M
authors: van Rijn
authors: F J
authors: FJ
authors: van Spronsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003710:Demography; D019937:Diagnostic Techniques and Procedures; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin