SPÁČIL, Zdeněk, AB KUMAR, HC LIAO, C AURAY-BLAIS, S STARK, TR SUHR, CR SCOTT, F TURECEK and MH GELB. Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples. Clinical Chemistry. Washington, USA: Amer. Assoc. Clinical Chemistry, vol. 62, No 1, p. 279-286. ISSN 0009-9147. doi:10.1373/clinchem.2015.245159. 2016.
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Basic information
Original name Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples
Authors SPÁČIL, Zdeněk, AB KUMAR, HC LIAO, C AURAY-BLAIS, S STARK, TR SUHR, CR SCOTT, F TURECEK and MH GELB.
Edition Clinical Chemistry, Washington, USA, Amer. Assoc. Clinical Chemistry, 2016, 0009-9147.
Other information
Original language English
Type of outcome Article in a journal
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 8.008
Doi http://dx.doi.org/10.1373/clinchem.2015.245159
UT WoS 000367703400037
Changed by Changed by: PharmDr. Zdeněk Spáčil, Ph.D., učo 238088. Changed: 29/9/2017 13:58.
Abstract
BACKGROUND: Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by deficiency in arylsulfatase A activity, leading to accumulation of sulfatide substrates. Diagnostic and monitoring procedures include demonstration of reduced arylsulfatase A activity in peripheral blood leukocytes or detection of sulfatides in urine. However, the development of a screening test is challenging because of instability of the enzyme in dried blood spots (DBS), the widespread occurrence of pseudodeficiency alleles, and the lack of available urine samples from newborn screening programs. METHODS: We measured individual sulfatide profiles in DBS and dried urine spots (DUS) from MLD patients with LC-MS/MS to identify markers with the discriminatory power to differentiate affected individuals from controls. We also developed a method for converting all sulfatide molecular species into a single species, allowing quantification in positive-ion mode upon derivatization. RESULTS: In DBS from MLD patients, we found up to 23.2-fold and 5.1-fold differences in total sulfatide concentrations for early- and late-onset MLD, respectively, compared with controls and pseudodeficiencies. Corresponding DUS revealed up to 164-fold and 78-fold differences for early- and late-onset MLD patient samples compared with controls. The use of sulfatides converted to a single species simplified the analysis and increased detection sensitivity in positive-ion mode, providing a second option for sulfatide analysis. CONCLUSIONS: This study of sulfatides in DBS and DUS suggests the feasibility of the mass spectrometry method for newborn screening of MLD and sets the stage for a larger-scale newborn screening pilot study. (C) 2015 American Association for Clinical Chemistry
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