title: Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency.
abstract: OBJECTIVE
  To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH).
  
  
  METHODS
  Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age ≥ 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels ≥ 6 mg/dL in all blood tests 1 year before inclusion. Blood samples were obtained the day before (day 1) and at 0, 4, 8 (day 2) and 24 h (day 3) after BH4 intake. Phe levels were measured using tandem mass spectrometry. The criteria used to define responsiveness to BH4 were: criterion 1- Phe reduction ≥ 30% 8 h after BH4 administration; criterion 2 - Phe reduction ≥ 30% 24 h after BH4 administration.
  
  
  RESULTS
  Eighteen patients were enrolled (median age, 14 years; 12 boys). Five patients were responsive to BH4, 3 according to both criteria (one classical PKU, two mild PKU); and two according to criterion 2 (one classical PKU; one indefinite PKU type). There were no differences between Phe serum levels on day 1 and at the other time points (p = 0.523). However, Phe levels on days 1 and 2 were significantly different (p = 0.006). The analysis of the phenotype-genotype association confirmed its multifactorial character.
  
  
  CONCLUSIONS
  A relevant number of Brazilian patients with HPA-PAH are responsive to BH4, in agreement with other studies in the literature.
authors.affiliation: Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Giugliani
authors.forename: Angela
authors.initials: A
authors.lastname: Sitta
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
authors.forename: Luiz C
authors.initials: LC
authors.lastname: Santana-da-Silva
authors.forename: Tatiéle
authors.initials: T
authors.lastname: Nalin
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ida Vanessa D
authors.initials: IV
authors.lastname: Schwartz
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000704:Analysis of Variance; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000178:diet therapy / Q000188:drug therapy* / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin