A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios.
J Lipid Res
; 58(5): 1002-1007, 2017 05.
Article
in En
| MEDLINE
| ID: mdl-28314860
ABSTRACT
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, tetrolt-CDCA and t-THCAtetrol, 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 tetrolt-CDCA ratio is an excellent derived biomarker for CTX that has the potential to be used in neonatal screening programs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Acids and Salts
/
Neonatal Screening
/
Xanthomatosis, Cerebrotendinous
/
Glucuronides
/
Dried Blood Spot Testing
Type of study:
Diagnostic_studies
/
Guideline
/
Screening_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Newborn
Language:
En
Journal:
J Lipid Res
Year:
2017
Type:
Article
Affiliation country:
Netherlands