title: [Tetrahydrobiopterin therapy for hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. When and how?].
abstract: BACKGROUND
  Some patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency respond with a variable decrease in plasma phenylalanine levels after oral tetrahydrobiopterin (BH4) administration and are then able to tolerate higher dietary phenylalanine intake or even to discontinue a phenylalanine-restricted diet. BH4-sensitive patients are usually identified by means of a BH4 loading test, but consensus on the methodology of this test and the interpretation of its results is lacking. Consequently, a simple tool to identify which patients are likely candidates for this treatment and how they will progress in the long-term is required.
  
  
  METHODS
  A combined oral BH4 loading test with phenylalanine (100 mg/kg) and BH4 (20 mg/kg) was performed in 20 patients with hyperphenylalaninemia under dietary phenylalanine restriction.
  
  
  RESULTS
  Independently of the genotype, the result was positive in all the 9 patients whose maximum phenylalanine level at diagnosis was below 815 nmol/ml. Currently, they are under treatment with tetrahydrobiopterin doses of 7-15 mg/kg/day. All these patients have been able to increase their oral phenylalanine intake. Six are currently following a normal diet and the remaining three are close to reaching this goal. None of the patients with a maximum phenylalanine level at diagnosis higher than 938 nmol/ml responded to the BH4 loading test.
  
  
  CONCLUSIONS
  The maximum phenylalanine level at diagnosis seems to be a simple and reliable method to predict response to BH4 treatment. A high percentage of BH4-sensitive patients are able to discontinue a phenylalanine-restricted diet after long-term tetrahydrobiopterin treatment.
authors.affiliation: Unidad de Enfermedades Metabólicas, Hospital Infantil Miguel Servet, Zaragoza, Spain. abaldellou@salud.aragon.es
authors.forename: A
authors.initials: A
authors.lastname: Baldellou Vázquez
authors.forename: María I
authors.initials: MI
authors.lastname: Salazar García-Blanco
authors.forename: María P
authors.initials: MP
authors.lastname: Ruiz-Echarri Zalaya
authors.forename: C
authors.initials: C
authors.lastname: Campos Calleja
authors.forename: L
authors.initials: L
authors.lastname: Ruiz Desviat
authors.forename: M
authors.initials: M
authors.lastname: Ugarte Pérez
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000172:deficiency* / Q000235:genetics; D010661:Phenylketonurias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D001708:Biopterins; D019001:Nitric Oxide Synthase; D010651:Phenylalanine Hydroxylase; C003402:sapropterin