Sulfatide Analysis by Mass Spectrometry for Screening of
Metachromatic Leukodystrophy in Dried Blood and Urine Samples

J 2016

Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples

SPÁČIL, Zdeněk; AB KUMAR; HC LIAO; C AURAY-BLAIS; S STARK et al.

Základní údaje

Originální název

Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples

Autoři

SPÁČIL, Zdeněk; AB KUMAR; HC LIAO; C AURAY-BLAIS; S STARK; TR SUHR; CR SCOTT; F TURECEK a MH GELB

Vydání

Clinical Chemistry, Washington, USA, Amer. Assoc. Clinical Chemistry, 2016, 0009-9147

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.008

Označené pro přenos do RIV

DOI

https://doi.org/10.1373/clinchem.2015.245159

UT WoS

000367703400037

Změněno: 29. 9. 2017 13:58, PharmDr. Zdeněk Spáčil, Ph.D.

Anotace

V originále

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

Citovat

SPÁČIL, Zdeněk; AB KUMAR; HC LIAO; C AURAY-BLAIS; S STARK; TR SUHR; CR SCOTT; F TURECEK a 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, 2016, roč. 62, č. 1, s. 279-286. ISSN 0009-9147. Dostupné z: https://doi.org/10.1373/clinchem.2015.245159.

@article{1391005,
   author = {Spáčil, Zdeněk and Kumar, AB and Liao, HC and AurayandBlais, C and Stark, S and Suhr, TR and Scott, CR and Turecek, F and Gelb, MH},
   article_location = {Washington, USA},
   article_number = {1},
   doi = {https://doi.org/10.1373/clinchem.2015.245159},
   language = {eng},
   issn = {0009-9147},
   journal = {Clinical Chemistry},
   title = {Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples},
   url = {http://dx.doi.org/10.1373/clinchem.2015.245159},
   volume = {62},
   year = {2016}
}

TY  - JOUR
ID  - 1391005
AU  - Spáčil, Zdeněk - Kumar, AB - Liao, HC - Auray-Blais, C - Stark, S - Suhr, TR - Scott, CR - Turecek, F - Gelb, MH
PY  - 2016
TI  - Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples
JF  - Clinical Chemistry
VL  - 62
IS  - 1
SP  - 279-286
EP  - 279-286
PB  - Amer. Assoc. Clinical Chemistry
SN  - 00099147
UR  - http://dx.doi.org/10.1373/clinchem.2015.245159
L2  - http://dx.doi.org/10.1373/clinchem.2015.245159
N2  - 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
ER  -

SPÁČIL, Zdeněk; AB KUMAR; HC LIAO; C AURAY-BLAIS; S STARK; TR SUHR; CR SCOTT; F TURECEK a MH GELB. Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples. \textit{Clinical Chemistry}. Washington, USA: Amer. Assoc. Clinical Chemistry, 2016, roč.~62, č.~1, s.~279-286. ISSN~0009-9147. Dostupné z: https://doi.org/10.1373/clinchem.2015.245159.

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