Individuals with phenylketonuria (PKU) lack the enzyme phenylalanine hydroxylase needed to metabolize phenylalanine (phe) and show elevated blood phe (>20 mg phe/dL) with normal protein intake. To prevent brain damage and cognitive impariment they must follow a lifelong, low-phe diet that is restricted in natural protein and requires ingestion of a bitter tasting amino acid formula. Unfortunately, most adolescents and adults with PKU go off the diet and show elevated blood phe levels. This is a clear risk for pregnant women with PKU whose infants show microcephaly, decreased IQ and/or congenital heart disease when exposed to maternal phe levels > 6-10 mg/dL. Glycomacropeptide (GMP) from cheese whey is uniquely suited to the PKU diet as it is the only known dietary protein that is naturally free of phe. A palatable alternative to the amino acid formula can be made with GMP. The long term goal is to assess the safety, efficacy and acceptability of GMP in the diet of subjects with PKU, 8 to 30 years of age.
The specific aims are: 1) to determine if a variety of palatable foods and beverages can be made with GMP to enhance variety, reduce cost and improve compliance with the PKU diet. Foods containing GMP will be developed in the Center for Dairy Research and sensory evaluation studies will be conducted in PKU subjects. 2) to determine if ingestion of a low-phe GMP diet will safely reduce blood phe levels and promote satiety compared to the conventional low-phe amino acid diet when dietary phe, total protein arid energy intake are held constant. Subjects with PKU (n=15; 5 each ages 8-12, 13-17 and 18-30 years) will be admitted to the General Clinical Research Center for a metabolic study conducted over 8 days. 3) Depending on the results of Aim 2, conduct a pilot study in 10 PKU subjects who follow the PKU diet but do not consume sufficient formula and show poor metabolic control. Data will help plan an outpatient clinical trial to determine if ingestion of a low-phe GMP diet will improve dietary adherence and metabolic control

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK071534-01
Application #
6954848
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (M4))
Program Officer
Mckeon, Catherine T
Project Start
2005-09-30
Project End
2007-07-31
Budget Start
2005-09-30
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$144,125
Indirect Cost
Name
University of Wisconsin Madison
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ney, Denise M; Blank, Robert D; Hansen, Karen E (2014) Advances in the nutritional and pharmacological management of phenylketonuria. Curr Opin Clin Nutr Metab Care 17:61-8
van Calcar, Sandra C; Ney, Denise M (2012) Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino Acid-based medical foods for nutrition management of phenylketonuria. J Acad Nutr Diet 112:1201-10
MacLeod, Erin L; Clayton, Murray K; van Calcar, Sandra C et al. (2010) Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria. Mol Genet Metab 100:303-8
Macleod, Erin L; Ney, Denise M (2010) Nutritional Management of Phenylketonuria. Ann Nestle Eng 68:58-69
MacLeod, Erin L; Gleason, Sally T; van Calcar, Sandra C et al. (2009) Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes. Mol Genet Metab 98:331-7
van Calcar, Sandra C; MacLeod, Erin L; Gleason, Sally T et al. (2009) Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. Am J Clin Nutr 89:1068-77
Laclair, Caitlin E; Ney, Denise M; MacLeod, Erin L et al. (2009) Purification and use of glycomacropeptide for nutritional management of phenylketonuria. J Food Sci 74:E199-206
Ney, D M; Gleason, S T; van Calcar, S C et al. (2009) Nutritional management of PKU with glycomacropeptide from cheese whey. J Inherit Metab Dis 32:32-9