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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


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0334-018X
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Volume 29, Issue 5

Issues

Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia – effect on median Phe/Tyr ratios

Mojca Zerjav Tansek
  • Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Urh Groselj
  • Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matic Kelvisar / Helena Kobe
  • Dietetics and Nutrition Unit, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Barbka Repic Lampret
  • Center for Laboratory Diagnostics, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia
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  • De Gruyter OnlineGoogle Scholar
/ Tadej Battelino
  • Corresponding author
  • Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia
  • Faculty of Medicine, Department of Pediatrics, University of Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-02-24 | DOI: https://doi.org/10.1515/jpem-2015-0337

Abstract

Background: Phenylalanine hydroxylase deficiency causes various degrees of hyperphenylalaninemia (HPA). Tetrahydrobiopterin (BH4; sapropterin) reduces phenylalanine (Phe) levels in responders, enabling relaxation of dietary therapy. We aimed to assess long-term effects of BH4 treatment in HPA patients.

Methods: Nine pre-pubertal BH4 responsive children were treated with BH4 for at least 2 years. The median dietary tolerance to Phe and levels of blood Phe, tyrosine (Tyr), zinc, selenium and vitamin B12 and anthropometric measurements, in the 2 years periods before and after the introduction of BH4 treatment were analyzed and compared. Adverse effects of BH4 were assessed.

Results: The daily Phe tolerance had tripled, from pretreatment median value of 620 mg (IQR 400–700 mg) to 2000 (IQR 1000–2000 mg) after 2 years of follow up (p<0.001). The median blood Phe levels during the 2 years period before introducing BH4 did not change significantly during the 2 years on therapy (from 200 μmol/L; IQR 191–302 to 190 μmol/L; IQR 135–285 μmol/L), but the median blood Phe/Tyr ratio had lowered significantly from pre-treatment value 4.7 to 2.4 during the 2 years on therapy (p=0.01). Median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change while on BH4 therapy (p=NS). No adverse effects were noticed.

Conclusions: BH4 therapy enabled patients much higher dietary Phe intakes, with no noticeable adverse effects. Median blood Phe and Tyr levels, median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change significantly on BH4 therapy, but median Phe/Tyr ratios had lowered.

Keywords: BH4, hyperphenylalaninemia; phenylketonuria; Phe/Tyr ratio; sapropterin

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About the article

Corresponding author: Tadej Battelino, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, UMC Ljubljana, Slovenia; and Faculty of Medicine, Department of Pediatrics, University of Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia, Fax: +386 1 2320190, E-mail:


Received: 2015-08-21

Accepted: 2015-12-30

Published Online: 2016-02-24

Published in Print: 2016-05-01


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 5, Pages 561–566, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0337.

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