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Clin Chim Acta. 2013 Oct 21;425:153-9. doi: 10.1016/j.cca.2013.06.027. Epub 2013 Jul 6.

Direct tandem mass spectrometric profiling of sulfatides in dry urinary samples for screening of metachromatic leukodystrophy.

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1
Institute of Inherited Metabolic Diseases, First Faculty of Medicine and General Teaching Hospital, Charles University, 128 08 Prague, Czech Republic.

Abstract

BACKGROUND:

Prediagnostic steps in suspected metachromatic leukodystrophy (MLD) rely on clinical chemical methods other than enzyme assays. We report a new diagnostic method which evaluates changes in the spectrum of molecular types of sulfatides (3-O-sulfogalactosyl ceramides) in MLD urine.

METHODS:

The procedure allows isolation of urinary sulfatides by solid-phase extraction on DEAE-cellulose membranes, transportation of a dry membrane followed by elution and tandem mass spectrometry (MS/MS) analysis in the clinical laboratory. Major sulfatide isoforms are normalized to the least variable component of the spectrum, which is the indigenous C18:0 isoform. This procedure does not require the use of specific internal standards and minimizes errors caused by sample preparation and measurement.

RESULTS:

Urinary sulfatides were analyzed in a set of 21 samples from patients affected by sulfatidosis. The combined abundance of the five most elevated isoforms, C22:0, C22:0-OH, C24:0, C24:1-OH, and C24:0-OH sulfatides, was found to give the greatest distinction between MLD-affected patients and a control group.

CONCLUSIONS:

The method avoids transportation of liquid urine samples and generates stable membrane-bound sulfatide samples that can be stored at ambient temperature. MS/MS sulfatide profiling targeted on the most MLD-representative isoforms is simple with robust results and is suitable for screening.

KEYWORDS:

ASA; CV; DEAE; DEAE-cellulose membrane; DUS; Diethylaminoethyl; Dry urinary samples; IPN; Isoforms; MLD; MS/MS; PTFE; Psap-d; S/N; SRM; Screening for metachromatic leukodystrophy; Tandem mass spectrometry; Urinary sulfatide; arylsulfatase A; coefficient of variation; dry urinary sample; isoform profile number (ratio of the sum of the major five isoforms and the C18:0 sulfatide); metachromatic leukodystrophy; polytetrafluoroethylene; prosaposin deficiency; selected reaction monitoring; signal to noise ratio; tandem mass spectrometry

PMID:
23838369
PMCID:
PMC3806293
DOI:
10.1016/j.cca.2013.06.027
[Indexed for MEDLINE]
Free PMC Article
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