Efficient analysis of urinary glycosaminoglycans by LC-MS/MS in mucopolysaccharidoses type I, II and VI
| Autor: | Christiane Auray-Blais, Yan An, Joe T.R. Clarke, David S. Millington, Haoyue H. Zhang, René Gagnon, Patrick Bherer, Sarah P. Young |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Adolescent Mucopolysaccharidosis I Endocrinology Diabetes and Metabolism Urinary system Dermatan Sulfate Urine Tandem mass spectrometry Biochemistry High-performance liquid chromatography Dermatan sulfate Glycosaminoglycan Young Adult chemistry.chemical_compound Endocrinology Reference Values Tandem Mass Spectrometry Genetics Humans Enzyme Replacement Therapy Child Molecular Biology Glycosaminoglycans Mucopolysaccharidosis II Creatinine Mucopolysaccharidosis VI Chromatography Infant Heparan sulfate chemistry Case-Control Studies Child Preschool Female Heparitin Sulfate Biomarkers Chromatography Liquid |
| Zdroj: | Molecular Genetics and Metabolism. 102:49-56 |
| ISSN: | 1096-7192 |
| Popis: | Mucopolysaccharidoses (MPSs) are complex storage disorders caused by specific lysosomal enzyme deficiencies, resulting in the accumulation of glycosaminoglycans (GAGs) in urine, plasma, as well as in various tissues. We devised and validated a straightforward, but accurate and precise tandem mass spectrometry methodology coupled to high performance liquid chromatography (LC-MS/MS) for the quantification of GAGs in urine. The method is applicable to the investigation of patients with MPS I, II, and VI, by quantifying dermatan sulfate (DS) and heparan sulfate (HS) in urine. We analyzed urine samples from 28 MPS patients, aged 1 to 42 years, and 55 control subjects (41 days to 18 years old). Levels of DS and HS in urine from healthy controls of all ages were below the limit of quantification. The levels of DS and HS in urine from 6 treated patients with MPS I were lower than in 6 untreated patients in DS (0.7-45 vs 9.3-177 mg/mmol creat) and HS (0-123 mg/mmol creatinine vs 38-418 mg/mmol creatinine); similar results were obtained for 9 patients with MPS II and 7 patients with MPS VI. Analyses were performed on as little as 250 μL of urine. Methanolysis took 75 min per sample; the total analysis run time for each LC-MS/MS injection was 8 min. Results indicate that the method is applicable to a wide variety of situations in which high accuracy and precision are required, including the evaluation of the effectiveness of existing and emerging treatments. |
| Databáze: | OpenAIRE |
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