title: Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan.
abstract: Tetrahydrobiopterin (BH(4)) deficiency is a rare, congenital and lethal condition resulting in phenylalanine build-up that can lead to mental retardation and developmental defects, unless properly treated. About 1 million newborn infants in Japan undergo neonatal PKU screening every year, of which about 1 in 2 million are diagnosed with the condition. In this post-marketing surveillance study, 19 patients with BH(4) deficiency in whom BH(4) supplementation with sapropterin dihydrochloride (Biopten®) (hereafter referred to as 'BH(4) therapy') was initiated before the age of 4 years, were followed up for ≤28 years. Patients who screened positive for BH(4) deficiency were treated with supplemental BH(4) plus L-dopa and 5-hydroxytryptophan. Data on the patients' clinical courses were collected once yearly at 10 medical centers in Japan. Seventeen patients were diagnosed with 6-pyruvoyl tetrahydropterin synthase deficiency and two with dihydropteridine reductase deficiency at an average age of 3.6 months; the mean age at end of follow-up was 14.6 years. Average duration of BH(4) therapy (mean dose, 5 mg/kg per day) was 13.2 years. Serum phenylalanine was reduced from more than 10 mg/dL at the start of drug administration to less than 2 mg/dL at end of follow-up. No abnormalities in height or weight were observed in any patients, except for one female patient with familial obesity. No unwarranted side effects were reported throughout the long-term course of treatment, even during pregnancy. BH(4) therapy can effectively maintain serum phenylalanine levels within the normal range in patients with BH(4) deficiency, and demonstrated excellent long-term safety, with no side effects.
authors: Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan. shintakuh@med.osaka-cu.ac.jp
authors: Haruo
authors: H
authors: Shintaku
authors: Misao
authors: M
authors: Ohwada
mesh_terms: D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000188:drug therapy / Q000209:etiology; D015259:Dopamine Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D007980:Levodopa / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D010661:Phenylketonurias / Q000145:classification / Q000188:drug therapy* / Q000235:genetics; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015259:Dopamine Agents; D001708:Biopterins; D007980:Levodopa; C003402:sapropterin