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
