Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses
Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A rang...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-08-01
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| Series: | Metabolites |
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| Online Access: | http://www.mdpi.com/2218-1989/4/3/655 |
| _version_ | 1818534963792838656 |
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| author | Shunji Tomatsu Tsutomu Shimada Robert W. Mason Adriana M. Montaño Joan Kelly William A. LaMarr Francyne Kubaski Roberto Giugliani Aratrik Guha Eriko Yasuda William Mackenzie Seiji Yamaguchi Yasuyuki Suzuki Tadao Orii |
| author_facet | Shunji Tomatsu Tsutomu Shimada Robert W. Mason Adriana M. Montaño Joan Kelly William A. LaMarr Francyne Kubaski Roberto Giugliani Aratrik Guha Eriko Yasuda William Mackenzie Seiji Yamaguchi Yasuyuki Suzuki Tadao Orii |
| author_sort | Shunji Tomatsu |
| collection | DOAJ |
| description | Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs. |
| first_indexed | 2024-12-11T18:18:29Z |
| format | Article |
| id | doaj.art-f1c6d7024dc24975b8e510fd50856ea4 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-12-11T18:18:29Z |
| publishDate | 2014-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-f1c6d7024dc24975b8e510fd50856ea42022-12-22T00:55:21ZengMDPI AGMetabolites2218-19892014-08-014365567910.3390/metabo4030655metabo4030655Establishment of Glycosaminoglycan Assays for MucopolysaccharidosesShunji Tomatsu0Tsutomu Shimada1Robert W. Mason2Adriana M. Montaño3Joan Kelly4William A. LaMarr5Francyne Kubaski6Roberto Giugliani7Aratrik Guha8Eriko Yasuda9William Mackenzie10Seiji Yamaguchi11Yasuyuki Suzuki12Tadao Orii13Nemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USANemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USANemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USADepartment of Pediatrics, Saint Louis University, St. Louis, MO 63104, USAAgilent Technologies, Inc., Wakefield, MA 01880, USAAgilent Technologies, Inc., Wakefield, MA 01880, USANemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USADepartment of Genetics/UFRGS, Medical Genetics Service/HCPA, Porto Alegre 90035-903, BrazilNemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USANemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USANemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USADepartment of Pediatrics, Shimane University, Shimane 693-8501, JapanMedical Education Development Center, Gifu University, Gifu 501-1194, JapanDepartment of Pediatrics, Gifu University, Gifu 501-1194, JapanMucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs.http://www.mdpi.com/2218-1989/4/3/655mucopolysaccharidosesELISAtandem mass spectrometryglycosaminoglycanchondroitin sulfatedermatan sulfateheparan sulfatekeratan sulfate |
| spellingShingle | Shunji Tomatsu Tsutomu Shimada Robert W. Mason Adriana M. Montaño Joan Kelly William A. LaMarr Francyne Kubaski Roberto Giugliani Aratrik Guha Eriko Yasuda William Mackenzie Seiji Yamaguchi Yasuyuki Suzuki Tadao Orii Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses Metabolites mucopolysaccharidoses ELISA tandem mass spectrometry glycosaminoglycan chondroitin sulfate dermatan sulfate heparan sulfate keratan sulfate |
| title | Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses |
| title_full | Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses |
| title_fullStr | Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses |
| title_full_unstemmed | Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses |
| title_short | Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses |
| title_sort | establishment of glycosaminoglycan assays for mucopolysaccharidoses |
| topic | mucopolysaccharidoses ELISA tandem mass spectrometry glycosaminoglycan chondroitin sulfate dermatan sulfate heparan sulfate keratan sulfate |
| url | http://www.mdpi.com/2218-1989/4/3/655 |
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