title: Individualized long-term outcomes in blood phenylalanine concentrations and dietary phenylalanine tolerance in 11 patients with primary phenylalanine hydroxylase (PAH) deficiency treated with Sapropterin-dihydrochloride.
abstract: We analyzed long-term sustainability of improved blood Phenylalanine (Phe) control and changes to dietary Phe tolerance in 11 patients (1 month to 16 years), with various forms of primary PAH deficiency (classic, moderate, severe phenylketonuria [PKU], mild hyperphenylalaninemia [HPA]), who were treated with 15-20mg/kg/d Sapropterin-dihydrochloride during a period of 13-44 months. 7/11 patients had a sustainable, significant reduction of baseline blood Phe concentrations and 6 of them also had an increase in mg/kg/day Phe tolerance. In 2 patients with mild HPA, blood Phe concentrations remained in the physiologic range even after a 22 and 36% increase in mg/kg/day Phe tolerance and an achieved Phe intake at 105% and 268% of the dietary reference intake (DRI) for protein. 2 of these responders had classic PKU. 1 patient with mild HPA who started treatment at 2 months of life, had a significant and sustainable reduction in pretreatment blood Phe concentrations, but no increase in the mg/kg/day Phe tolerance. An increase in Phe tolerance could only be demonstrated when expressing the patient's daily Phe tolerance with the DRI for protein showing an increase from 58% at baseline to 78% of normal DRI at the end of the observation. Long-term follow-up of patients with an initial response to treatment with Sapropterin is essential to determine clinically meaningful outcomes. Phenylalanine tolerance should be expressed in mg/kg/day and/or % of normal DRI to differentiate medical therapy related from physiologic growth related increase in daily Phe intake.
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada. Electronic address: sstockler@cw.bc.ca.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stockler-Ipsiroglu
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yuskiv
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Ramona
authors.initials: R
authors.lastname: Salvarinova
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Delia
authors.initials: D
authors.lastname: Apatean
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Alette
authors.initials: A
authors.lastname: Giezen
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lillquist
authors.affiliation: Department of Pediatrics, University of British Columbia, Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004032:Diet; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D063868:Patient Outcome Assessment; D010649:Phenylalanine / Q000008:administration & dosage* / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy*; D064167:Recommended Dietary Allowances; D013997:Time Factors
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
keywords: Cofactor; Medical nutrition therapy; Outcome; Pharmacologic therapy; Tetrahydrobiopterin