title: Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy.
abstract: OBJECTIVE
  Sapropterin is an oral synthetic formulation of tetrahydrobiopterin prescribed as adjunctive therapy for phenylketonuria. The efficacy of sapropterin in reducing blood phenylalanine levels has been demonstrated in clinical studies of individuals with phenylketonuria older than 4 years of age. Its effect on neurocognitive functioning in younger children has not been examined.
  
  
  METHODS
  A 2-year interim analysis of blood phenylalanine levels, prescribed dietary phenylalanine intake, and neurocognitive functioning was performed in children who started receiving sapropterin at 0-6 years of age and responded with a ≥30% mean blood phenylalanine reduction. Children were evaluated at baseline and 2-year follow-up.
  
  
  RESULTS
  Sapropterin had a favorable safety profile and lowered blood phenylalanine levels with increased prescribed dietary phenylalanine intakes. Mean full-scale intelligence quotient was 103 ± 12 at baseline and 104 ± 10 at 2-year follow-up (P = 0.50, paired t-test, n = 25). For children younger than 30 months of age, the cognitive composite score from the Bayley Scales of Infant and Toddler Development, Third Edition, remained within the average range.
  
  
  CONCLUSIONS
  Sapropterin had a favorable safety profile, was effective in lowering blood phenylalanine levels while clinically requiring dietary adjustment, resulting in increased phenylalanine intake, and preserved neurocognitive performance in children who started therapy between 0 and 6 years of age.
authors.affiliation: Department of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.affiliation: Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Komudi
authors.initials: K
authors.lastname: Siriwardena
authors.affiliation: Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Annette
authors.initials: A
authors.lastname: Feigenbaum
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dimmock
authors.affiliation: The Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.affiliation: British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stockler
authors.affiliation: Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Waisbren
authors.affiliation: BioMarin Pharmaceutical, Inc., Novato, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Lang
authors.affiliation: BioMarin Pharmaceutical, Inc., Novato, California, USA.
authors.forename: Elaina
authors.initials: E
authors.lastname: Jurecki
authors.affiliation: BioMarin Pharmaceutical, Inc., Novato, California, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Zhang
authors.affiliation: BioMarin Pharmaceutical, Inc., Novato, California, USA.
authors.forename: Suyash
authors.initials: S
authors.lastname: Prasad
mesh_terms: D001708:Biopterins / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin