title: Advances in the nutritional and pharmacological management of phenylketonuria.
abstract: OBJECTIVE
  The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU).
  
  
  RESULTS
  Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phenylalanine (phe) intact protein that represents a new dietary alternative to synthetic amino acids for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an amino acid diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin, acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral amino acids inhibit phe transport across the intestinal mucosa and blood-brain barrier, and are most effective for individuals unable to comply with the low-phe diet.
  
  
  CONCLUSIONS
  Although a low-phe synthetic amino acid diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to amino acid formula that may improve bone health, and tetrahydrobiopterin permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management.
authors.affiliation: aDepartment of Nutritional Sciences, Waisman Center, University of Wisconsin-Madison, Madison bDepartment of Medicine, Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee cDepartment of Medicine, Division of Rheumatology, University of Wisconsin School of Medicine and Public Health, Madison, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ney
authors.forename: Robert D
authors.initials: RD
authors.lastname: Blank
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hansen
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002364:Caseins / Q000032:analysis / Q000494:pharmacology; D019587:Dietary Supplements; D006801:Humans; D008894:Milk Proteins / Q000032:analysis / Q000494:pharmacology; D009154:Mutation; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000235:genetics / Q000378:metabolism; D010661:Phenylketonurias / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014443:Tyrosine / Q000378:metabolism; D000067816:Whey Proteins
chemical_list: D000596:Amino Acids; D002364:Caseins; D008894:Milk Proteins; D010446:Peptide Fragments; D000067816:Whey Proteins; C065989:caseinomacropeptide; D001708:Biopterins; D014443:Tyrosine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; C003402:sapropterin