Conditions: Phenylketonuria
Keywords: Phenylketonuria PKU tetrahydrobiopterin sapropterin dihydrochloride BH4 Kuvan Oxidative stress
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 12
Healthy volunteers: yes

Brief summary:
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).

Detailed description:
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.

Arms:
arm 1: Participants in this group have PKU and were deemed unresponsive to the drug. They will attend their first study visit, and proceed through the meal challenge without BH4. They will then take BH4 for 2 weeks. The second meal challenge will be performed with the participant's final dose of BH4. arm 2: Participants in this group match an enrolled PKU participant in terms of age, gender, and body mass index class. They will participate in a single study visit and will not be given BH4. arm 3: Participants in this group will use their already prescribed BH4 with the meal challenge and be assessed at a single study visit. They will take their prescribed BH4 with the meal.

Interventions: intervention 1: Kuvan intervention 2: Meal Challenge
Intervention descriptions: intervention 1: Participants in the BH4 Non-Responder group will be given a 20 mg/kg body weight/day dose of Kuvan to take on a daily basis for two weeks. The last dose will be administered at the participant's study visit 2. intervention 2: At each study visit, patients will receive a meal high in polyunsaturated fats that will promote a transitory increase in oxidative stress measures and endothelial dysfunction

Protocol document: