title: The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply.
abstract: OBJECTIVE
  BH4-sensitive phenylketonuria (PKU) patients relax their phenylalanine (Phe) restricted diet due to increased Phe tolerance, while keeping dried blood Phe concentrations with in the therapeutic range. We aimed to investigate metabolic control, eating habits and nutrient supply under long-term BH4-therapy.
  
  
  METHODS
  Retrospective analysis of mean dried blood Phe concentrations and their variability, food and nutrient intake in BH4-sensitive patients (n = 8, 3f, age 6.0-16.6 y) under classical dietary treatment for one year and during the three years after initiation of BH4.
  
  
  RESULTS
  Phe concentrations of BH4-sensitve PKU patients remained within therapeutic range throughout the observation period, independent of therapeutic regime. Under BH4, Phe tolerance increased significantly (493.2 ± 161.8 mg/d under classical diet vs 2021.93 ± 897.4 mg/d two years under BH4; P = 0.004). Variability of Phe concentrations remained unchanged (mean SD; P = 1.000). Patients adjust their food choice and significantly increased their intake of cereals, potatoes, dairy products and meat (P = 0.019, P = 0.016, P = 0.016 and P = 0.016, respectively). Under diet changes after implementation of BH4 a drop in micronutrient intake (vitamin D, folic acid, iron, calcium, iodine) could be revealed (P = 0.005, P < 0.001, P = 0.004, P = 0.001, P = 0.003, respectively).
  
  
  CONCLUSIONS
  BH4-sensitive PKU patients can achieve good metabolic control under an adjuvant BH4- or a BH4 monotherapy. The liberalized diet under BH4 seems to jeopardize the quality of patients' nutrition, and these patients require close follow-up and special nutrition education to minimize the risk for imbalanced diet and nutrient deficiencies.
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Alena G
authors.initials: AG
authors.lastname: Thiele
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rohde
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mütze
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Arelin
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Liebigstraße 27, 04103 Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Liebigstraße 27, 04103 Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: Department of Internal Medicine, University Hospitals, University of Leipzig, Liebigstraße 20, 04103 Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Baerwald
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.affiliation: Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health, University Hospitals, University of Leipzig, Liebigstraße 20 a, 04103 Leipzig, Germany.
authors.forename: Skadi
authors.initials: S
authors.lastname: Beblo
keywords: AAM, amino acid mixture; BH4, tetrahydrobiopterin; PKU, phenylketonuria; Phe, phenylalanine