title: The neonatal tetrahydrobiopterin loading test in phenylketonuria: what is the predictive value?
abstract: BACKGROUND
  It is unknown whether the neonatal tetrahydrobiopterin (BH4) loading test is adequate to diagnose long-term BH4 responsiveness in PKU. Therefore we compared the predictive value of the neonatal (test I) versus the 48-h BH4 loading test (test II) and long-term BH4 responsiveness.
  
  
  METHODS
  Data on test I (>1991, 20 mg/kg) at T = 8 (n = 85) and T = 24 (n = 5) were collected and compared with test II and long-term BH4 responsiveness at later age, with ≥30% Phe decrease used as the cut-off.
  
  
  RESULTS
  The median (IQR) age at hospital diagnosis was 9 (7-11) days and the age at test II was 11.8 (6.6-13.7) years. The baseline Phe concentrations at test I were significantly higher compared to test II (1309 (834-1710) versus 514 (402-689) μmol/L, respectively, P = 0.000). 15/85 patients had a positive test I T = 8. All, except one patient who was not tested for long-term BH4 responsiveness, showed long-term BH4 responsiveness. In 20/70 patients with a negative test I T = 8, long-term BH4 responsiveness was confirmed. Of 5 patients with a test I T = 24, 1/5 was positive at both tests and showed long-term BH4 responsiveness, 2/5 had negative results at both tests and 2/5 showed a negative test I T = 24, but a positive test II with 1/2 showing long-term BH4 responsiveness.
  
  
  CONCLUSIONS
  Both a positive neonatal 8- and 24-h BH4 loading test are predictive for long-term BH4 responsiveness. However, a negative test does not rule out long-term BH4 responsiveness. Other alternatives to test for BH4 responsiveness at neonatal age should be investigated.
authors.affiliation: University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, PO box 30.001, CA33, 9700 RB, Groningen, The Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: Anjema
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Floris C
authors.initials: FC
authors.lastname: Hofstede
authors.affiliation: Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands.
authors.forename: Annet M
authors.initials: AM
authors.lastname: Bosch
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.affiliation: Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Maaike C
authors.initials: MC
authors.lastname: de Vries
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carolien C A
authors.initials: CC
authors.lastname: Boelen
authors.affiliation: University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, PO box 30.001, CA33, 9700 RB, Groningen, The Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: van Rijn
authors.affiliation: University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, PO box 30.001, CA33, 9700 RB, Groningen, The Netherlands. f.j.van.spronsen@umcg.nl.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D002648:Child; D003955:Diagnostic Tests, Routine; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010661:Phenylketonurias / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001708:Biopterins; C003402:sapropterin
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