Phenylketonuria, Oxidative Stress, and BH4

The Ability of Kuvan® (Sapropterin Dihydrochloride) to Prevent Meal-induced Lipid Peroxidation and Endothelial Dysfunction in Patients With Phenylketonuria: a Pilot Study

The purpose of this study is to see how tetrahydrobiopterin therapy (BH4; also known as sapropterin dihydrochloride or Kuvan) affects measures of oxidative stress and endothelial function in patients with Phenylketonuria (PKU).

Oxidative stress will be induced by having participants eat a meal in polyunsaturated fats. The investigators will see how participants respond to the meal challenge over the course of 6 hours.

• PKU participants who are currently on BH4 therapy will be evaluated while taking BH4 with the meal at a single study visit.
• PKU participants who did not responded to BH4 therapy will be evaluated twice. At the first study visit the investigators will see how you react to the meal challenge when you are not given BH4. You will be given BH4 for two weeks, then return for a second meal challenge study visit while taking BH4.
• Healthy controls will be evaluated after consuming the meal only (no BH4) at a single study visit.

Inclusion Criteria:

• Have read, understood, and signed this consent form (and assent form, if <18 years old)
• Are between the ages of 10-45 years
• Weigh at least 75 pounds (34 kg)
• Meet group-specific criteria

Exclusion Criteria:

• Smoke
• Have any history of cardiovascular disease
• Have hepatic impairment, or demonstrate abnormal baseline liver function lab test results
• Have donated blood within 3 months prior to the study or are anemic as shown by the baseline lab results
• Are unwilling to discontinue dietary supplements (excluding medical food) two weeks prior to their first study visit
• Are currently take medications that will interfere with the interpretation of selected endpoints (such as lipid-lowering medication)
• Are currently pregnant or breastfeeding
• Excluding PKU, have a chronic illness, disorder, or condition (including but not limited to diabetes, hypertension, cancer)
• Have taken any investigational drug (including Kuvan for Kuvan-unresponsive participants & controls) within 3 months prior to the study
• In the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures