@article{91fdd1c746c94a37abb95391be69fff1,
title = "Newborn screening for Cerebrotendinous Xanthomatosis: A retrospective biomarker study using both flow-injection and UPLC-MS/MS analysis in 20,000 newborns",
abstract = "Background and aims: Cerebrotendinous Xanthomatosis (CTX) is a treatable disorder of bile acid synthesis caused by deficiency of 27-sterol hydroxylase -encoded by CYP27A1- leading to gastrointestinal and progressive neuropsychiatric symptoms. Biochemically, CTX is characterized by accumulation of the bile alcohol cholestanetetrol glucuronide (GlcA-tetrol) and the deficiency of tauro-chenodeoxycholic acid (t-CDCA) and tauro-trihydroxycholestanoic acid (t-THCA). Materials and Methods: To ascertain the feasibility of CTX newborn screening (NBS) we performed a study with deidentified Dutch dried blood spots using reagents and equipment that is frequently used in NBS laboratories. 20,076 deidentified newborn blood spots were subjected to flow-injection (FIA)-MS/MS and UPLC-MS/MS analysis to determine the concentration of GlcA-tetrol and calculate the GlcA-tetrol/t-CDCA and t-THCA/GlcA-tetrol ratios. Results: Using UPLC-MS/MS analysis both GlcA-tetrol concentration and/or metabolite ratios GlcA-tetrol/t-CDCA proved to be informative biomarkers; newborn DBS results did not overlap with those of the CTX patients. For FIA-MS/MS, GlcA-tetrol also was an excellent marker but when using the combination of the GlcA-tetrol/t-CDCA and t-THCA/GlcA-tetrol ratios also did not yield any screen positives. Conclusion: Newborn screening for CTX using only metabolite ratios following the measurement of three CTX biomarkers is possible using either FIA-MS/MS or UPLC-MS/MS, which paves the way for introduction of CTX NBS.",
keywords = "Cerebrotendinous Xanthomatosis, Metabolite ratios, Newborn screening, Tandem mass spectrometry",
author = "Vaz, {Fr{\'e}d{\'e}ric M.} and Youssra Jamal and Rob Barto and Gelb, {Michael H.} and DeBarber, {Andrea E.} and Wevers, {Ron A.} and Nelen, {Marcel R.} and Aad Verrips and Bootsma, {Albert H.} and Bouva, {Marelle J.} and Nick Kleise and {van der Zee}, Walter and Tao He and Salomons, {Gajja S.} and Huidekoper, {Hidde H.}",
note = "Funding Information: This work was supported by ZonMw, project “Validation of a newborn screening method for Cerebrotendinous Xanthomatosis”, number 543002008. We would like to thank the Radboud Genome Technology Center (RGTC) for helping with DBS DNA purifications and subsequent whole-exome sequencing. RGTC is part of the Netherlands X-omics Initiative and partially funded by NWO (The Netherlands Organization for Scientific Research; project 184.034.019). We are grateful to Travere Therapeutics for providing GlcA-tetrol and 2H6-GlcA-tetrol internal standard. Funding Information: This work was supported by ZonMw, project “Validation of a newborn screening method for Cerebrotendinous Xanthomatosis”, number 543002008. We would like to thank the Radboud Genome Technology Center (RGTC) for helping with DBS DNA purifications and subsequent whole-exome sequencing. RGTC is part of the Netherlands X-omics Initiative and partially funded by NWO (The Netherlands Organization for Scientific Research; project 184.034.019). We are grateful to Travere Therapeutics for providing GlcA-tetrol and 2 H 6 -GlcA-tetrol internal standard. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2023",
month = jan,
day = "15",
doi = "https://doi.org/10.1016/j.cca.2022.12.011",
language = "English",
volume = "539",
pages = "170--174",
journal = "Clinica Chimica Acta",
issn = "0009-8981",
publisher = "Elsevier",
}