Influence of PAH Genotype on Sapropterin Response in PKU: Results of a Single-Center Cohort Study.

ABSTRACT:

Objective

Identifying phenylalanine hydroxylase (PAH) mutations associated with sapropterin response in phenylketonuria (PKU) would be an advantageous means to determine clinical benefit to sapropterin therapy.

Methods

Sapropterin response, defined as a ≥30 % reduction in phenylalanine (Phe) levels after a dose of 10 mg/kg/day sapropterin for week one and 20 mg/kg/day for week two in 112 PKU patients aged 4-45 years, was assessed in an outpatient setting. PAH was sequenced in all patients. Mutations were correlated with sapropterin response. Dietary Phe intake was increased over a 6-week period in responsive patients.

Results

Forty-six of 112 patients were sapropterin responsive. Genotypes p.[L48S];[L48S] and p.[Y414C];[Y414C] were always associated with response at a

SUBMITTER: Leuders S 

PROVIDER: S-EPMC4110336 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature