Use of Glycerol Phenylbutyrate (Ravicti™) as a Chaperone to Stabilize Enzyme in Patients With MCAD Deficiency Due to the Common MCAD 985A>G (K304E) Mutation

Participation in the study will require one overnight admission and three outpatient visits at the Clinical and Translational Research Center at Children's Hospital of Pittsburgh of UPMC (also called the PCTRC). The total length of the study is 7 weeks.

Subjects will have blood work and an intravenous access line (IV) placed for several blood draws during the visit. Subjects will begin fasting at 8pm during the admission, which means they may consume only non-caloric fluids (water, unsweetened black coffee or tea, or sugar-free beverages). The next morning, fasting blood work will be obtained. The subject can then eat breakfast and will receive the study drug, Ravicti. The total time of fasting will be 12 hours.

Dosing for this study will begin at 2 grams/m2/day, which is about one-fifth (1/5) the dose used for other disorders. The reason for starting the dose lower in MCAD patients is that Ravicti is metabolized by the MCAD enzyme. Following the initial dose, blood will be drawn from the IV every two hours for 8 hours. These blood studies will check the levels of Ravicti in the subject's blood and monitor how the subject's body metabolizes them. The subject will be discharged 8 hours after drug administration. Following discharge, the subject will take Ravicti every day for two weeks.

Visit 2: After two weeks at a dose of 2 grams/m2/day, the subject will fast after 8 PM, and will come to the PCTRC the following morning to have an IV placed and blood draws. If the subject's blood work from the first visit shows that there is no concern, the subject's dose will be increased to 4 grams/m2/day. The subject will receive the first dose at this level in the PCTRC with breakfast, and blood samples will be collected from the IV every 2 hours for the next 8 hours. The subject will continue on this dose for two weeks.

Visit 3: After two weeks at a dose of 4 grams/m2/day, the subject will fast after 8 PM, and will come to the PCTRC the following morning to have an IV placed and blood draws. If the subject's blood work from the previous visit shows that there is no concern, the subject's dose will be increased to 6 grams/m2/day. The subject will receive the first dose at this level in the PCTRC with breakfast, and blood samples will be collected from the IV every 2 hours for the next 8 hours. The subject will continue on this dose for two weeks.