The Effectiveness of Kuvan in Amish PKU Patients

Study Summary

The purpose of this study is to determine if Amish patients with PKU show responsiveness after a high dose, prolonged Saproterin trial. The population of interest has a high frequency of a specific splice site mutation, the 1066-11G\>A mutation. This splice site mutation activates a cryptic splice site resulting in an in frame insertion of 9 nucleotides preceding exon 11. This leads to protein conformational changes and abrogation of function. Previous studies of this genotype have indicated \<1% residual activity of the PAH enzyme and an insignificant responsiveness to Saproterin. However, in this specific study Phe levels were evaluated only over 24 hours after a single-dose BH4 challenge at the standard dose of 20mg/kg. Based on new clinical information, the investigators hypothesize that if given a prolonged trial of Saproterin at a higher dose, Amish patients with PKU, specifically those homozygous for the c.1066-11G\>A mutation, will have a significant reduction in Phe levels or an increase in Phe tolerance and/or improvement in executive functioning and quality of life.

Primary Outcome

Subjects will be assessed for plasma Phe concentration by dried blood spot cards during their initial visit (day 1) and every week thereafter. Except during the two week wash-out period where no plasma Phe will be collected. A decrease of plasma Phe levels from baseline by 20% will be considered a positive response.

Conditions Studied

Interventions

• DRUG saproterin dihydrochloride
• OTHER Diet treatment

Study Locations (1)