title: Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life.
abstract: BACKGROUND
  Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4).
  
  
  METHODS
  Based on the review of neonatal BH(4) test results and mutation analysis in 41 PKU patients, 19 were identified as potentially BH(4)-sensitive (9 females, 10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL(®)) beginning from 1 year before, during the first 42 days, and after 3 months of BH(4) therapy.
  
  
  RESULTS
  Eight BH(4)-sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p = 1.0). Six of them were able to stop dietary protein restriction entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable to age-matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH(4) supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders.
  
  
  CONCLUSIONS
  BH(4) can allow PKU patients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL(®), partly due to high scores even before BH(4) therapy. Specific questionnaires should be developed for inborn metabolic disorders.
authors.affiliation: University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ziesch
authors.forename: J
authors.initials: J
authors.lastname: Weigel
authors.forename: A
authors.initials: A
authors.lastname: Thiele
authors.forename: U
authors.initials: U
authors.lastname: Mütze
authors.forename: C
authors.initials: C
authors.lastname: Rohde
authors.forename: U
authors.initials: U
authors.lastname: Ceglarek
authors.forename: J
authors.initials: J
authors.lastname: Thiery
authors.forename: W
authors.initials: W
authors.lastname: Kiess
authors.forename: S
authors.initials: S
authors.lastname: Beblo
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy*; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires
chemical_list: D004044:Dietary Proteins; D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin