Sponsored by: Singh Research Group Emory University Department of Human Genetics Information about BH4: What it is and how it works Updated on November 20 th, 2008

Kuvan TM is a pharmaceutical (prescription drug) with a structure very similar to a natural compound humans make called Tetrahydrobiopterin (BH4). Kuvan TM comes in pill form and is usually taken once a day with meals. Response to Kuvan TM is currently defined by the medical community as a 30% or greater decrease in plasma Phe levels. Approximately 50% of all people with PKU respond this way to Kuvan TM. Both severe and mild forms of PKU can respond to Kuvan TM, however, those with milder forms of PKU do have a greater chance of responding General Information about BH4

BH4 Molecule Structures BH4 (Tetrahydrobiopterin) As it is naturally made by the body Kuvan TM (Sapropterin Dihydrochloride) Pharmaceutical with structure similar to natural BH4 Reference for structures:

Phenylalanine (Phe) and Tyrosine (Tyr) are essential amino acids that the body must have to function properly. But too much of these amino acids in the blood can be toxic. BH4 is a cofactor naturally made by the body which the PAH (phenylalanine hydroxylase) enzyme uses to convert Phe into Tyr. For most people, this keeps the body’s Phe and Tyrosine in a healthy balance. How BH4 works to convert Phe to Tyrosine PAH BH4 PheTyr

People with PKU make the same amount of natural BH4 as people without PKU. However, in PKU the PAH enzyme is malformed and does not function very well. This can cause Phe to increase to toxic levels inside the body. Providing extra BH4, in the form of Kuvan TM, has been shown to increase the ability of the defective PAH enzyme to convert Phe into Tyrosine for some people who have PKU How can taking Kuvan TM help someone with PKU? BH4 PheTyr BH4

At the Emory Genetics Clinic: 1.We obtain a baseline plasma Phe level 2.You are prescribed 20mg/kg/day dose of Kuvan TM 3.For the next several days you must not change your diet or formula. 4.Your blood Phe levels will be checked several times during this period to look for a response to Kuvan TM 5.A response to the medicine can take anywhere from two days to 4 weeks How do I know if I would respond to Kuvan TM ?

PKU – Kuvan TM – The BH4 and PKU clinical trial at Emory –You can contact the research coordinator Mary Jane Kennedy ( ). –You may also visit the BH4 and PKU study website: Where can I find more information about…?