Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research
Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to...
Ausführliche Beschreibung
Autor*in: |
Michel van Weeghel [verfasserIn] Lindsey Welling [verfasserIn] Eileen P. Treacy [verfasserIn] Ronald J. A. Wanders [verfasserIn] Sacha Ferdinandusse [verfasserIn] Annet M. Bosch [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2018 |
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Übergeordnetes Werk: |
In: Orphanet Journal of Rare Diseases - BMC, 2006, 13(2018), 1, Seite 7 |
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Übergeordnetes Werk: |
volume:13 ; year:2018 ; number:1 ; pages:7 |
Links: |
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DOI / URN: |
10.1186/s13023-018-0888-1 |
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Katalog-ID: |
DOAJ054434025 |
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245 | 1 | 0 | |a Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research |
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520 | |a Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. | ||
650 | 4 | |a Classical galactosemia | |
650 | 4 | |a Galactose metabolites | |
650 | 4 | |a Fibroblasts | |
650 | 4 | |a UDP-galactose | |
650 | 4 | |a Galactose-1-phosphate | |
650 | 4 | |a Galactose oxidation | |
653 | 0 | |a Medicine | |
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700 | 0 | |a Lindsey Welling |e verfasserin |4 aut | |
700 | 0 | |a Eileen P. Treacy |e verfasserin |4 aut | |
700 | 0 | |a Ronald J. A. Wanders |e verfasserin |4 aut | |
700 | 0 | |a Sacha Ferdinandusse |e verfasserin |4 aut | |
700 | 0 | |a Annet M. Bosch |e verfasserin |4 aut | |
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10.1186/s13023-018-0888-1 doi (DE-627)DOAJ054434025 (DE-599)DOAJa06bd86a5c7e415885e733c80910623c DE-627 ger DE-627 rakwb eng Michel van Weeghel verfasserin aut Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. Classical galactosemia Galactose metabolites Fibroblasts UDP-galactose Galactose-1-phosphate Galactose oxidation Medicine R Lindsey Welling verfasserin aut Eileen P. Treacy verfasserin aut Ronald J. A. Wanders verfasserin aut Sacha Ferdinandusse verfasserin aut Annet M. Bosch verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 7 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:7 https://doi.org/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/article/a06bd86a5c7e415885e733c80910623c kostenfrei http://link.springer.com/article/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 7 |
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10.1186/s13023-018-0888-1 doi (DE-627)DOAJ054434025 (DE-599)DOAJa06bd86a5c7e415885e733c80910623c DE-627 ger DE-627 rakwb eng Michel van Weeghel verfasserin aut Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. Classical galactosemia Galactose metabolites Fibroblasts UDP-galactose Galactose-1-phosphate Galactose oxidation Medicine R Lindsey Welling verfasserin aut Eileen P. Treacy verfasserin aut Ronald J. A. Wanders verfasserin aut Sacha Ferdinandusse verfasserin aut Annet M. Bosch verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 7 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:7 https://doi.org/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/article/a06bd86a5c7e415885e733c80910623c kostenfrei http://link.springer.com/article/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 7 |
allfields_unstemmed |
10.1186/s13023-018-0888-1 doi (DE-627)DOAJ054434025 (DE-599)DOAJa06bd86a5c7e415885e733c80910623c DE-627 ger DE-627 rakwb eng Michel van Weeghel verfasserin aut Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. Classical galactosemia Galactose metabolites Fibroblasts UDP-galactose Galactose-1-phosphate Galactose oxidation Medicine R Lindsey Welling verfasserin aut Eileen P. Treacy verfasserin aut Ronald J. A. Wanders verfasserin aut Sacha Ferdinandusse verfasserin aut Annet M. Bosch verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 7 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:7 https://doi.org/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/article/a06bd86a5c7e415885e733c80910623c kostenfrei http://link.springer.com/article/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 7 |
allfieldsGer |
10.1186/s13023-018-0888-1 doi (DE-627)DOAJ054434025 (DE-599)DOAJa06bd86a5c7e415885e733c80910623c DE-627 ger DE-627 rakwb eng Michel van Weeghel verfasserin aut Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. Classical galactosemia Galactose metabolites Fibroblasts UDP-galactose Galactose-1-phosphate Galactose oxidation Medicine R Lindsey Welling verfasserin aut Eileen P. Treacy verfasserin aut Ronald J. A. Wanders verfasserin aut Sacha Ferdinandusse verfasserin aut Annet M. Bosch verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 7 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:7 https://doi.org/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/article/a06bd86a5c7e415885e733c80910623c kostenfrei http://link.springer.com/article/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 7 |
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10.1186/s13023-018-0888-1 doi (DE-627)DOAJ054434025 (DE-599)DOAJa06bd86a5c7e415885e733c80910623c DE-627 ger DE-627 rakwb eng Michel van Weeghel verfasserin aut Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. Classical galactosemia Galactose metabolites Fibroblasts UDP-galactose Galactose-1-phosphate Galactose oxidation Medicine R Lindsey Welling verfasserin aut Eileen P. Treacy verfasserin aut Ronald J. A. Wanders verfasserin aut Sacha Ferdinandusse verfasserin aut Annet M. Bosch verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 13(2018), 1, Seite 7 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:13 year:2018 number:1 pages:7 https://doi.org/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/article/a06bd86a5c7e415885e733c80910623c kostenfrei http://link.springer.com/article/10.1186/s13023-018-0888-1 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 7 |
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profiling of intracellular metabolites produced from galactose and its potential for galactosemia research |
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Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research |
abstract |
Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. |
abstractGer |
Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. |
abstract_unstemmed |
Abstract Background Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-13C]-labeled galactose. Methods GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls. The following metabolites were analyzed: [U13C]-galactose, [U13C]-galactose-1-phosphate (Gal-1-P) and [13C6]- uridine diphosphate(UDP)-galactose. The ratio of [U13C]-Gal-1-P/ [13C6]-UDP-galactose was defined as the galactose index (GI). Results All patient cell lines could be distinguished from the control cell lines and there was a clear difference between variant and classical patients. Variant patients had lower levels of [U13C]-galactose and [U13C]-Gal-1-P than classical patients (though substantially higher than healthy controls) and higher levels of [13C6]-UDP-galactose than classical patients (though substantially lower than healthy controls) resulting in a different GI in all groups. Conclusions GMP in fibroblasts is a sensitive method to determine residual galactose metabolism capacity, which can discriminate between patients with a classical presentation of galactosemia, patients with a variant presentation and healthy controls. GMP may be a useful method for early prognostication after further validation in a larger cohort of patients representing the full phenotypic spectrum of galactosemia. |
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Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research |
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https://doi.org/10.1186/s13023-018-0888-1 https://doaj.org/article/a06bd86a5c7e415885e733c80910623c http://link.springer.com/article/10.1186/s13023-018-0888-1 https://doaj.org/toc/1750-1172 |
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Lindsey Welling Eileen P. Treacy Ronald J. A. Wanders Sacha Ferdinandusse Annet M. Bosch |
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