Denise M Ney1, Robert D Blank, Karen E Hansen. 1. 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.
Abstract
PURPOSE OF REVIEW: The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). RECENT FINDINGS: 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 murinePKU 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. SUMMARY: 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: M Dangin; Y Boirie; C Garcia-Rodenas; P Gachon; J Fauquant; P Callier; O Ballèvre; B Beaufrère Journal: Am J Physiol Endocrinol Metab Date: 2001-02 Impact factor: 4.310
Authors: Lindsay C Burrage; Judy McConnell; Rebecca Haesler; Mary Ann O'Riordan; V Reid Sutton; Douglas S Kerr; Shawn E McCandless Journal: Mol Genet Metab Date: 2012-07-16 Impact factor: 4.797
Authors: Stefanie Keil; Karen Anjema; Francjan J van Spronsen; Nilo Lambruschini; Alberto Burlina; Amaya Bélanger-Quintana; Maria L Couce; Francois Feillet; Roberto Cerone; Amelie S Lotz-Havla; Ania C Muntau; Annet M Bosch; Concetta A P Meli; Thierry Billette de Villemeur; Ilse Kern; Enrica Riva; Marcello Giovannini; Lena Damaj; Vincenzo Leuzzi; Nenad Blau Journal: Pediatrics Date: 2013-05-20 Impact factor: 7.124
Authors: Emily A Sawin; Travis J De Wolfe; Busra Aktas; Bridget M Stroup; Sangita G Murali; James L Steele; Denise M Ney Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-08-06 Impact factor: 4.052
Authors: Luis Aldámiz-Echevarría; Marta Llarena; María A Bueno; Jaime Dalmau; Isidro Vitoria; Ana Fernández-Marmiesse; Fernando Andrade; Javier Blasco; Carlos Alcalde; David Gil; María C García; Domingo González-Lamuño; Mónica Ruiz; María A Ruiz; Luis Peña-Quintana; David González; Felix Sánchez-Valverde; Lourdes R Desviat; Belen Pérez; María L Couce Journal: J Hum Genet Date: 2016-04-28 Impact factor: 3.172
Authors: M J Pena; M F de Almeida; E van Dam; K Ahring; A Bélanger-Quintana; K Dokoupil; H Gokmen-Ozel; A M Lammardo; A MacDonald; M Robert; J C Rocha Journal: Eur J Clin Nutr Date: 2016-04-27 Impact factor: 4.016
Authors: Denise M Ney; Bridget M Stroup; Murray K Clayton; Sangita G Murali; Gregory M Rice; Frances Rohr; Harvey L Levy Journal: Am J Clin Nutr Date: 2016-07-13 Impact factor: 7.045
Authors: Felipe Pinheiro de Oliveira; Roberta Hack Mendes; Priscila Thiago Dobbler; Volker Mai; Victor Salter Pylro; Sheldon G Waugh; Filippo Vairo; Lilia Farret Refosco; Luiz Fernando Würdig Roesch; Ida Vanessa Doederlein Schwartz Journal: PLoS One Date: 2016-06-23 Impact factor: 3.240