title: Smith-Lemli-Opitz syndrome diagnosed by using time-of-flight secondary-ion mass spectrometry.
abstract: We describe a rapid and sensitive method involving time-of-flight secondary-ion mass spectrometry (TOF-SIMS) for specific laboratory diagnosis of the Smith-Lemli-Opitz syndrome, which is characterized by massive (approximately 1000-fold) accumulation of the biosynthetic cholesterol precursor 7-dehydrocholesterol. Minute amounts of blood (1-50 microL) were extracted with n-hexane, and aliquots were analyzed by TOF-SIMS. 7-Dehydrocholesterol and its isomers were detected at 491.3 mass units ([M + 107Ag]+) and cholesterol at 495.3 mass units ([M + 109Ag]+). Quantitation of 7-dehydrocholesterol and cholesterol was achieved after saponification and addition of stigmasterol as internal standard. Whereas 7-dehydrocholesterol and isomeric dehydrocholesterol were not detectable in controls, the patients revealed concentrations ranging between 0.84 and 1.25 mmol/L. Comparison with results obtained by gas chromatography indicated that quantitation by TOF-SIMS yielded the sum of 7-dehydrocholesterol, isomeric dehydrocholesterol II, and sterol III, the latter two also being increased in the patients. Consistent with quantitation by gas chromatography, the cholesterol concentrations in the patients ranged between 1.54 and 2.12 mmol/L (controls: 6.10 +/- 1.37 mmol/L).
authors.affiliation: Instituten für Arterioskleroseforschung, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Seedorf
authors.forename: M
authors.initials: M
authors.lastname: Fobker
authors.forename: R
authors.initials: R
authors.lastname: Voss
authors.forename: K
authors.initials: K
authors.lastname: Meyer
authors.forename: F
authors.initials: F
authors.lastname: Kannenberg
authors.forename: D
authors.initials: D
authors.lastname: Meschede
authors.forename: K
authors.initials: K
authors.lastname: Ullrich
authors.forename: J
authors.initials: J
authors.lastname: Horst
authors.forename: A
authors.initials: A
authors.lastname: Benninghoven
authors.forename: G
authors.initials: G
authors.lastname: Assmann
mesh_terms: D002784:Cholesterol / Q000097:blood; D002849:Chromatography, Gas; D003684:Dehydrocholesterols / Q000097:blood*; D006586:Hexanes; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis*; D013058:Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D012016:Reference Values; D012680:Sensitivity and Specificity; D013265:Stigmasterol; D013577:Syndrome
chemical_list: D003684:Dehydrocholesterols; D006586:Hexanes; C026385:n-hexane; D002784:Cholesterol; D013265:Stigmasterol; C016705:7-dehydrocholesterol