Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III
Mucolipidosis type II and III (MLII/III) is caused by defects in the mannose-6-phosphate system, which is essential to target most of the lysosomal hydrolases to the lysosome. MLII/III patients present with marked elevations in the activities of most lysosomal enzymes in plasma, but their profiles i...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426923000241 |
| _version_ | 1797822092532514816 |
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| author | Xinying Hong Laura Pollard Miao He Michael H. Gelb Timothy C. Wood |
| author_facet | Xinying Hong Laura Pollard Miao He Michael H. Gelb Timothy C. Wood |
| author_sort | Xinying Hong |
| collection | DOAJ |
| description | Mucolipidosis type II and III (MLII/III) is caused by defects in the mannose-6-phosphate system, which is essential to target most of the lysosomal hydrolases to the lysosome. MLII/III patients present with marked elevations in the activities of most lysosomal enzymes in plasma, but their profiles in dried blood spots (DBS) have not been well described. In the current study, we measured the activities of 12 lysosomal enzymes in DBS, among which acid sphingomyelinase, iduronate-2-sulfatase, and alpha-N-acetylglucosaminidase were significantly elevated in MLII/III patients when compared to random newborns. This sets the stage for using DBS to diagnose MLII/III. Furthermore, given an increasing number of lysosomal storage disorders are being included in the recommended uniform screening panel, our results also indicate that population-based newborn screening for MLII/III can be implemented with minimal efforts. |
| first_indexed | 2024-03-13T10:03:53Z |
| format | Article |
| id | doaj.art-f8d8131cceb34bbabd6f04c30932cba0 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-03-13T10:03:53Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-f8d8131cceb34bbabd6f04c30932cba02023-05-23T04:21:50ZengElsevierMolecular Genetics and Metabolism Reports2214-42692023-06-0135100978Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and IIIXinying Hong0Laura Pollard1Miao He2Michael H. Gelb3Timothy C. Wood4Department of Chemistry, University of Washington, Seattle, WA, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Corresponding author: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, 5NW59, Main Building, 34th Street & Civic Center Blvd., Philadelphia, PA, 19104, USA.Greenwood Genetic Center, Greenwood, SC, USADepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USADepartment of Chemistry, University of Washington, Seattle, WA, USA; Department of Biochemistry, University of Washington, Seattle, WA, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus/Children's Hospital of Colorado, Aurora, CO, USAMucolipidosis type II and III (MLII/III) is caused by defects in the mannose-6-phosphate system, which is essential to target most of the lysosomal hydrolases to the lysosome. MLII/III patients present with marked elevations in the activities of most lysosomal enzymes in plasma, but their profiles in dried blood spots (DBS) have not been well described. In the current study, we measured the activities of 12 lysosomal enzymes in DBS, among which acid sphingomyelinase, iduronate-2-sulfatase, and alpha-N-acetylglucosaminidase were significantly elevated in MLII/III patients when compared to random newborns. This sets the stage for using DBS to diagnose MLII/III. Furthermore, given an increasing number of lysosomal storage disorders are being included in the recommended uniform screening panel, our results also indicate that population-based newborn screening for MLII/III can be implemented with minimal efforts.http://www.sciencedirect.com/science/article/pii/S2214426923000241Mucolipidosis type II and III (MLII/III)Dried blood spots (DBS)Lysosomal storage disorders (LSDs)Enzymatic activityNewborn screening |
| spellingShingle | Xinying Hong Laura Pollard Miao He Michael H. Gelb Timothy C. Wood Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III Molecular Genetics and Metabolism Reports Mucolipidosis type II and III (MLII/III) Dried blood spots (DBS) Lysosomal storage disorders (LSDs) Enzymatic activity Newborn screening |
| title | Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III |
| title_full | Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III |
| title_fullStr | Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III |
| title_full_unstemmed | Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III |
| title_short | Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III |
| title_sort | multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of mucolipidosis type ii and iii |
| topic | Mucolipidosis type II and III (MLII/III) Dried blood spots (DBS) Lysosomal storage disorders (LSDs) Enzymatic activity Newborn screening |
| url | http://www.sciencedirect.com/science/article/pii/S2214426923000241 |
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