title: Mutational and oxidative stress analysis in patients with mucopolysaccharidosis type I undergoing enzyme replacement therapy.
abstract: BACKGROUND
  Mucopolysaccharidosis type I (MPS I) patients present a wide range of clinical manifestations, which could be due to the high molecular heterogeneity of the IDUA gene and to pathological events besides the enzyme deficiency. The aim of this study was to identify the most common MPS I causing mutations and to evaluate some oxidative stress markers in Brazilian patients.
  
  
  METHODS
  3 common mutations in the IDUA gene were searched in 11 MPS I patients by PCR-RFLP. Activities of antioxidant enzymes catalase and superoxide dismutase, and levels of total glutathione and thiobarbituric acid reactive substances were evaluated by spectrophotometric and colorimetric methods, during different periods of enzyme replacement therapy.
  
  
  RESULTS
  The most common mutations were P533R and W402X, with allelic frequencies of 33.33% and 27.8% respectively. MPS I patients presented high levels of lipid peroxidation and enzyme replacement therapy led to an increase of catalase and a decrease of superoxide dismutase activities.
  
  
  CONCLUSIONS
  P533R and W402X accounted for more than 60% of the alleles, but no genotype-phenotype correlation could be established. The alterations in antioxidant enzyme activities suggest that oxidative stress may be an important event among MPS I patients, which could contribute to the physiopathology of the disease.
authors.affiliation: Institute of Genetics and Inborn Errors of Metabolism (IGEIM), Department of Pediatrics, Universidade Federal de São Paulo, São Paulo - Brazil. nessagp@yahoo.com.br
authors.forename: Vanessa Gonçalves
authors.initials: VG
authors.lastname: Pereira
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.forename: Cecília
authors.initials: C
authors.lastname: Micheletti
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
mesh_terms: D005260:Female; D005787:Gene Frequency; D006801:Humans; D007068:Iduronidase / Q000235:genetics / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D007068:Iduronidase