title: [Genotyping and treatment modification in patients with phenylketonuria: an introduction to pharmacogenomics].
abstract: BACKGROUND
  Phenylketonuria is the most common inborn error of metabolism. The disease is caused by mutations of the phenylalanine hydroxylase gene, decreasing or completely abolishing the activity of the encoded enzyme. Treatment consists in maintaining low blood phenylalanine concentration. Untreated patients develop mental retardation. Use of tetrahydrobiopterin is a new, alternative treatment method, effective in some phenylketonuria-patients. Because the dietary treatment becomes less restrictive in such patients, quality of life rises in them substantially. Phenylketonuria-causing mutations strictly determine susceptibility to tetrahydrobiopterin in a given patient.
  
  
  OBJECTIVE
  The aim of the study was to select candidates for tetrahydrobiopterin treatment basing on analysis of detected mutations of the phenylalanine hydroxylase gene.
  
  
  METHODS
  Phenylketonuria-patients from Krakow region were genotyped by means of PCR, DHPLC and sequencing.
  
  
  RESULTS
  95% of mutations of the phenylalanine hydroxylase gene were identified in a group of 238 phenylketonuria-patients followed up in Krakow region. A genotype excluding treatment with tetrahydrobiopterin was find in >53% of patients. In 23% of patients genotypes were found which were typical for milder forms of the disease (far less restrictive dietary treatment needed in comparison with patients with classical phenylketonuria). Approximately half of the remaining patients could probably benefit from use of dietary treatment with additional tetrahydrobiopterin supplementation.
authors.affiliation: Katedra Pediatrii Collegium Medicum, Uniwersytetu Jagiellońskiego, Kraków. AgMir@mp.pl
authors.forename: Mirosław
authors.initials: M
authors.lastname: Bik-Multanowski
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Pietrzyk
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019587:Dietary Supplements; D005838:Genotype; D006801:Humans; D009154:Mutation; D010649:Phenylalanine / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000178:diet therapy / Q000188:drug therapy* / Q000235:genetics*; D011788:Quality of Life
chemical_list: D001708:Biopterins; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; C003402:sapropterin