Prevalence of (potentially) BH4 responsive mutations in PKU patients from Ghent, Belgium.

As preliminary study to set out the effectiveness of BH4 therapy in our population of PKU patients, we studied their mutations and compared this with reported BH4 responsive mutations in the literature. From 41 of 52 (78%) followed PKU patients detailed genetic information was available. We detected 27 different mutations in the 82 alleles of these patients. All of the mutations fond were previously reported in PKU patients. The most common mutation is the splicing mutation IVS12nt1, the most common in Caucasians (10 out of 82 mutations, 12%). This is followed by R158Q (7/82, 9%), the IVS10nt546 splicing mutation (8/82, 7%) and the R261Q (8/82, 7%) mutation. The G272X, R243Q and L48S mutations share a common fourth place (4/82, 5%). Interestingly, all mutations present in this top four are potentially associated with BH4 responsiveness. Moreover, 33 from the 41 patients (80%) have at least one mutation potentially associated with BH4 responsiveness. Furthermore our cohort has four patients homozygous for the same PAH mutation, one P225T, one R261Q and two R243Q. R243Q and R261Q are potential BH4 responsive mutations, and these three patients can help to further asses the BH4 responsiveness of this mutation. Conclusion: a very high percentage from our PKU patients is potentially BH4 responsive. We will start to asses BH4 responsiveness with a BH4 loading test in the four homozygous patients, and in the 26 patients with two potential BH4 responsive mutations.

Jaar van publicatie:2008

Trefwoorden:PKU, BH4, BH4 responsive mutations