title: Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness.
abstract: Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might require a very expensive trial treatment with BH4 or prolonged BH4-loading procedures. The selection of patients eligible for BH4-therapy by means of genotyping of the PAH gene mutations may be recommended as a complementary approach. A population-wide genotyping study was carried out in 1286 Polish phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover prospectively the treatment by a National Health Fund. A total of 95 types of mutations were identified. Genetic variants corresponding with probable BH4-responsiveness were found in 28.2% of cases. However, patients with mild or classical phenylketonuria who require continuous treatment accounted for 11.4% of the studied population only. Analysis of the published data shows similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe. Therefore, it can be concluded, that the proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region.
authors.affiliation: Chair of Pediatrics, Jagiellonian University, Krakow, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Bik-Multanowski
authors.affiliation: Department of Pediatric Gastroenterology and Metabolism, Medical University, Poznan, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kaluzny
authors.affiliation: Voivodeship Hospital, Wroclaw, Poland;
authors.forename: Renata
authors.initials: R
authors.lastname: Mozrzymas
authors.affiliation: Institute of Mother and Child, Warszawa, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Oltarzewski
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Polish Mother's Health Memorial Institute, Lodz, Poland;
authors.forename: Ewa
authors.initials: E
authors.lastname: Starostecka
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Polish Mother's Health Memorial Institute, Lodz, Poland;
authors.forename: Agata
authors.initials: A
authors.lastname: Lange
authors.affiliation: Chair of Pediatrics, Jagiellonian University, Krakow, Poland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Didycz
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gizewska
authors.affiliation: Department of Pediatrics, Oncology and Endocrinology, Medical University, Gdansk.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Ulewicz-Filipowicz
authors.affiliation: Voivodeship Hospital, Bydgoszcz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chrobot
authors.affiliation: Department of Pediatrics and Developmental Disorders in Children and Adolescents, Medical University in Bialystok, Poland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Mikoluc
authors.affiliation: PRA International, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymczakiewicz-Multanowska
authors.affiliation: Department of Pediatric Gastroenterology and Metabolism, Medical University, Poznan, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Cichy
authors.affiliation: Chair of Pediatrics, Jagiellonian University, Krakow, Poland.
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Pietrzyk
mesh_terms: D054316:Biomarkers, Pharmacological; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010649:Phenylalanine / Q000172:deficiency / Q000235:genetics; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000188:drug therapy* / Q000235:genetics; D011044:Poland
chemical_list: D054316:Biomarkers, Pharmacological; D001708:Biopterins; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; C003402:sapropterin