title: Long-term follow-up of patients with phenylketonuria receiving tetrahydrobiopterin treatment.
abstract: Treatment with tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH4-responsive phenylketonuria (PKU). A number of studies has reported on the short-term BH4 treatment of patients with PKU, but long-term data are lacking. Here, we describe the effects of long-term treatment with BH4 on 16 patients, who showed a >28% reduction in blood Phe following testing for BH4 overload. The mean dose of BH4 was 16 mg/kg body weight (range 5-36 mg/kg body weight). The mean treatment duration was 56 months (range 24-110 months). Of 16 patients, 14 achieved long-term Phe control with BH4 treatment, with a mean blood Phe concentration of 321 ± 236 µmol/l. The mean decrease from baseline in blood Phe levels in these 14 patients was 54.6%. Of the seven patients who required continued dietary restriction, Phe intake increased from 200-300 mg/day to 800-1000 mg/day. Factors that may cause fluctuation of Phe levels in BH4-treated patients include patients' PAH genotype, Phe intake, changes in protein catabolism or anabolism, and periods of illness or infection.
authors.affiliation: Klinik für Kinder und Jungendmedizin, Reutlingen, Klinik am Steinenberg, Steinenbergstrasse 31, Reutlingen 72764, Germany. trefz_f@kreiskliniken-reutlingen.de
authors.forename: Friedrich K
authors.initials: FK
authors.lastname: Trefz
authors.forename: D
authors.initials: D
authors.lastname: Scheible
authors.forename: G
authors.initials: G
authors.lastname: Frauendienst-Egger
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018753:Diet, Protein-Restricted; D054796:Drug Dosage Calculations; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin