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Mutational and oxidative stress analysis in patients with mucopolysaccharidosis type I undergoing enzyme replacement
Vanessa Gonçalves Pereira1, Ana Maria Martins, Cecília Micheletti
1Institute of Genetics and Inborn Errors of Metabolism (IGEIM), Department of Pediatrics, Universidade Federal de São Paulo, São Paulo - Brazil. nessagp@yahoo.com.br
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.
Insights
Two common mutations, P533R and W402X, explain over 60% of Mucopolysaccharidosis type I (MPS I) alleles in Brazilian patients. Oxidative stress markers suggest this plays a role in MPS I pathology.
Area of Science:
- Genetics
- Biochemistry
- Medical Research
Background:
- Mucopolysaccharidosis type I (MPS I) exhibits diverse clinical symptoms potentially linked to IDUA gene mutations and other pathological factors.
- Investigating common mutations and oxidative stress in MPS I patients is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify prevalent IDUA gene mutations causing MPS I in Brazilian patients.
- To assess oxidative stress markers in MPS I patients undergoing enzyme replacement therapy.
Main Methods:
- Genotyping of 11 MPS I patients for three common IDUA mutations using PCR-RFLP.
- Quantification of antioxidant enzyme activities (catalase, superoxide dismutase) and oxidative stress markers (glutathione, TBARS) via spectrophotometric and colorimetric assays.
Main Results:
- P533R and W402X mutations were identified as the most common, with allelic frequencies of 33.33% and 27.8%, respectively.
- MPS I patients showed elevated lipid peroxidation; enzyme replacement therapy modulated catalase and superoxide dismutase activity.
Conclusions:
- P533R and W402X mutations account for over 60% of MPS I alleles studied, though genotype-phenotype correlation was not established.
- Observed alterations in antioxidant enzyme activities indicate that oxidative stress is a significant factor in MPS I pathophysiology.
