A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S]
Cerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis in which symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520338360 |
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| author | Frédéric M. Vaz Albert H. Bootsma Willem Kulik Aad Verrips Ron A. Wevers Peter C. Schielen Andrea E. DeBarber Hidde H. Huidekoper |
| author_facet | Frédéric M. Vaz Albert H. Bootsma Willem Kulik Aad Verrips Ron A. Wevers Peter C. Schielen Andrea E. DeBarber Hidde H. Huidekoper |
| author_sort | Frédéric M. Vaz |
| collection | DOAJ |
| description | Cerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis in which symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed a new dried blood spot (DBS) screening assay for this disorder on the basis of different ratios between the accumulating cholestanetetrol glucuronide (tetrol) and specific bile acids/bile acid intermediates, without the need for derivatization. A quarter-inch DBS punch was extracted with methanol, internal standards were added, and after concentration the extract was injected into the tandem mass spectrometer using a 2 min flow injection analysis for which specific transitions were measured for cholestanetetrol glucuronide, taurochenodeoxycholic acid (t-CDCA), and taurotrihydroxycholestanoic acid (t-THCA). A proof-of-principle experiment was performed using 217 Guthrie cards from healthy term/preterm newborns, CTX patients, and Zellweger patients. Using two calculated biomarkers, tetrol:t-CDCA and t-THCA:tetrol, this straightforward method achieved an excellent separation between DBSs of CTX patients and those of controls, Zellweger patients, and newborns with cholestasis. The results of this small pilot study indicate that the tetrol:t-CDCA ratio is an excellent derived biomarker for CTX that has the potential to be used in neonatal screening programs. |
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| id | doaj.art-149f04e1e52c4d299760cb20acaf0e0e |
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| language | English |
| last_indexed | 2024-12-14T03:19:24Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-149f04e1e52c4d299760cb20acaf0e0e2022-12-21T23:19:04ZengElsevierJournal of Lipid Research0022-22752017-05-0158510021007A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S]Frédéric M. Vaz0Albert H. Bootsma1Willem Kulik2Aad Verrips3Ron A. Wevers4Peter C. Schielen5Andrea E. DeBarber6Hidde H. Huidekoper7To whom correspondence should be addressed.; Department of Clinical Chemistry and Pediatrics, Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The NetherlandsDepartment of Clinical Chemistry and Pediatrics, Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The NetherlandsDepartment of Clinical Chemistry and Pediatrics, Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The NetherlandsDepartment of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The NetherlandsDepartment of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Centre, Nijmegen, The NetherlandsCentre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, The NetherlandsDepartment of Physiology and Pharmacology, Oregon Health and Science University, Portland, ORDepartment of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The NetherlandsCerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis in which symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed a new dried blood spot (DBS) screening assay for this disorder on the basis of different ratios between the accumulating cholestanetetrol glucuronide (tetrol) and specific bile acids/bile acid intermediates, without the need for derivatization. A quarter-inch DBS punch was extracted with methanol, internal standards were added, and after concentration the extract was injected into the tandem mass spectrometer using a 2 min flow injection analysis for which specific transitions were measured for cholestanetetrol glucuronide, taurochenodeoxycholic acid (t-CDCA), and taurotrihydroxycholestanoic acid (t-THCA). A proof-of-principle experiment was performed using 217 Guthrie cards from healthy term/preterm newborns, CTX patients, and Zellweger patients. Using two calculated biomarkers, tetrol:t-CDCA and t-THCA:tetrol, this straightforward method achieved an excellent separation between DBSs of CTX patients and those of controls, Zellweger patients, and newborns with cholestasis. The results of this small pilot study indicate that the tetrol:t-CDCA ratio is an excellent derived biomarker for CTX that has the potential to be used in neonatal screening programs.http://www.sciencedirect.com/science/article/pii/S0022227520338360bile acid metabolismbile acids and salts biosynthesisinborn errors of metabolismtandem mass spectrometryCYP27A1 |
| spellingShingle | Frédéric M. Vaz Albert H. Bootsma Willem Kulik Aad Verrips Ron A. Wevers Peter C. Schielen Andrea E. DeBarber Hidde H. Huidekoper A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] Journal of Lipid Research bile acid metabolism bile acids and salts biosynthesis inborn errors of metabolism tandem mass spectrometry CYP27A1 |
| title | A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] |
| title_full | A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] |
| title_fullStr | A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] |
| title_full_unstemmed | A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] |
| title_short | A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios[S] |
| title_sort | newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios s |
| topic | bile acid metabolism bile acids and salts biosynthesis inborn errors of metabolism tandem mass spectrometry CYP27A1 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520338360 |
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