title: Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy.
abstract: The clinical, nutritional, and neuropsychological data of 11 mild/moderate PKU patients after one year of treatment with BH4 are evaluated. BH4 monotherapy was introduced at 5 mg/kg/day in 14 PKU patients. In 11/14 patients, Phe tolerance increased significantly from 356+/-172 to 1546+/-192 mg/day (p=0.004), and special PKU formula was gradually reduced until complete removal. In them, mean plasma Phe concentrations remained below 360 micromol/L at 5 mg BH4/kg/day (7 mg/kg/day in one patient). BH4 therapy was stopped in three patients (V388M/P362T and R243Q/IVS10-11G>A genotypes) because it was not possible to improve Phe tolerance and to remove formula intake. Serum micronutrients were not significantly different at the start of treatment and at one year follow-up, except for selenium, which increased significantly after one year of therapy (p=0.017). Anthropometric, and nutritional measurements were within the age- and sex-specific percentiles for a healthy population after one year therapy. Neuropsychological follow-up indicated that intelligence scores persisted within normal limits. In terms of patients' genotype, we confirmed that the P275S mutation combined with R408W was associated with long-term BH4 responsiveness, while the combination of P362T/V388M, and R243Q/IVS10-11G>A resulted in poor metabolic control in long-term BH4 therapy. In summary, our data confirm that BH4 is a safe, and effective therapy in a selected group of mild, and moderate PKU patients who respond to the BH4 loading test. Low doses of BH4 in monotherapy permit withdrawal of the special formula and guarantee a good clinical and nutritional outcome with no adverse side effects in PKU patients.
authors.affiliation: Nutrition Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Nilo
authors.initials: N
authors.lastname: Lambruschini
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez-Dueñas
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: Anna
authors.initials: A
authors.lastname: Mas
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.forename: Rosa
authors.initials: R
authors.lastname: Gassió
authors.forename: Lilian
authors.initials: L
authors.lastname: Gómez
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Jaume
authors.initials: J
authors.lastname: Campistol
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D049628:Body Size; D002648:Child; D002675:Child, Preschool; D018753:Diet, Protein-Restricted; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin