The neonatal tetrahydrobiopterin loading test in phenylketonuria: what is the predictive value?

Karen Anjema, Floris C. Hofstede, Annet M. Bosch, M. Estela Rubio-Gozalbo, Maaike C. de Vries, Carolien C. A. Boelen, Margreet van Rijn, Francjan J. van Spronsen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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) mu mol/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.

Original languageEnglish
Article number10
Number of pages5
JournalOrphanet journal of rare diseases
Volume11
DOIs
Publication statusPublished - 29-Jan-2016

Keywords

  • Phenylketonuria
  • PKU
  • Tetrahydrobiopterin
  • BH4
  • Neonate
  • LONG-TERM TREATMENT
  • PHENYLALANINE-HYDROXYLASE
  • FOLLOW-UP
  • HYPERPHENYLALANINEMIA
  • RESPONSIVENESS
  • SAPROPTERIN
  • CHILDREN
  • THERAPY

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