Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose


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KOR D., Yilmaz B. Ş. , BULUT F. D. , CEYLANER S. , Mungan N. Ö.

Journal of Pediatric Endocrinology and Metabolism, vol.30, no.7, pp.713-718, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 7
  • Publication Date: 2017
  • Doi Number: 10.1515/jpem-2016-0461
  • Title of Journal : Journal of Pediatric Endocrinology and Metabolism
  • Page Numbers: pp.713-718
  • Keywords: BH4, divided daily doses, phenylketonuria, PHENYLALANINE-HYDROXYLASE DEFICIENCY, MOUSE MODEL, DIHYDROCHLORIDE, MUTATIONS, STABILITY

Abstract

© 2017 Walter de Gruyter GmbH, Berlin/Boston.Background: Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. Methods: After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Results: Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. Conclusions: When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.