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Advances in the nutritional and pharmacological management of phenylketonuria

Ney, Denise M.a; Blank, Robert D.b; Hansen, Karen E.c

Current Opinion in Clinical Nutrition & Metabolic Care: January 2014 - Volume 17 - Issue 1 - p 61–68
doi: 10.1097/MCO.0000000000000002
PROTEIN, AMINO ACID METABOLISM AND THERAPY: Edited by Olav Rooyackers and John Brosnan

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.

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

Correspondence to Denise M. Ney, Department of Nutritional Sciences, 1415 Linden Dr Madison, WI 53706-1571, USA. Tel: +1 608 262 4386; fax: +1 608 262 4386; e-mail:

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