Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness.

Miroslaw Bik-Multanowski; Lukasz Kaluzny; Renata Mozrzymas; Mariusz Oltarzewski; Ewa Starostecka; Agata Lange; Bozena Didycz; Maria Gizewska; Jolanta Ulewicz-Filipowicz; Agnieszka Chrobot; Bozena Mikoluc; Agnieszka Szymczakiewicz-Multanowska; Wojciech Cichy; Jacek J Pietrzyk

doi:10.18388/abp.2013_2029

Miroslaw Bik-Multanowski Chair of Pediatrics, Jagiellonian University, Krakow, Poland.;
Lukasz Kaluzny Department of Pediatric Gastroenterology and Metabolism, Medical University, Poznan, Poland.;
Renata Mozrzymas Voivodeship Hospital, Wroclaw, Poland;;
Mariusz Oltarzewski Institute of Mother and Child, Warszawa, Poland.;
Ewa Starostecka Department of Endocrinology and Metabolic Diseases, Polish Mother's Health Memorial Institute, Lodz, Poland;;
Agata Lange Department of Endocrinology and Metabolic Diseases, Polish Mother's Health Memorial Institute, Lodz, Poland;;
Bozena Didycz Chair of Pediatrics, Jagiellonian University, Krakow, Poland.;
Maria Gizewska Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, Szczecin, Poland.;
Jolanta Ulewicz-Filipowicz Department of Pediatrics, Oncology and Endocrinology, Medical University, Gdansk.;
Agnieszka Chrobot Voivodeship Hospital, Bydgoszcz, Poland.;
Bozena Mikoluc Department of Pediatrics and Developmental Disorders in Children and Adolescents, Medical University in Bialystok, Poland.;
Agnieszka Szymczakiewicz-Multanowska PRA International, Warsaw, Poland.;
Wojciech Cichy Department of Pediatric Gastroenterology and Metabolism, Medical University, Poznan, Poland.;
Jacek J Pietrzyk Chair of Pediatrics, Jagiellonian University, Krakow, Poland.;

DOI: https://doi.org/10.18388/abp.2013_2029

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.