Biochemical profiling to predict disease severity in metachromatic leukodystrophy

Tan, Mohd Adi Firdaus; Fuller, Maria; Zabidi-Hussin, Z A M H; Hopwood, John J.; Meikle, Peter J.

doi:10.1016/j.ymgme.2009.09.006

Cited by 23 publications

(25 citation statements)

References 24 publications

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“…Utilizing the C18:0 isoform as a normalizing parameter avoids isotope or mass-labeled external standards that are commonly used in other methods [24, 25, 27]. In addition, the C18:0 reference isoform is naturally present in the analyzed material along with the measured isoforms and thus compensates for errors caused by sample processing, e.g., affinity binding, elution and extraction, and also for matrix effects [39].…”

Section: Discussionmentioning

confidence: 99%

“…Previous bioanalytical methods of sulfatide detection were based on thin layer chromatography separation of native glycosphingolipids with densitometric evaluation [20], or utilized chemical derivatization combined with gas [21] or liquid [22] chromatography, or applied matrix-assisted laser desorption ionization mass spectrometry after sulfatide conversion into its lyso-form [23]. Recently, Meikle's group reported detection and quantitation of urine sulfatides by electrospray ionization mass spectrometry in the negative ion mode [24, 25]. Norris et al [26] have developed an assay for sulfatide detection in brain tissue that was based on positive ion electrospray tandem mass spectrometry of sulfatide-lithium ion adducts.…”

Section: Introductionmentioning

confidence: 99%

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

Kuchař

Asfaw

Poupětová

et al. 2013

Clinica Chimica Acta

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Background Prediagnostic steps in suspected metachromatic leukodystrophy (MLD) rely onclinical 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kuchař

Asfaw

Poupětová

et al. 2013

Clinica Chimica Acta

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“…The level of residual catabolic activity is one out of several factors contributing to the molecular pathogenesis and clinical form of the disease. In the threshold theory, a correlation between functional residual catabolic activity and the progression of the lipid storage disease has been formulated Sandhoff 1983 -1984), which was basically confirmed for different clinical forms of diseases such as metachromatic leukodystrophy (Leinekugel et al 1992;Tan et al 2010), GM2-gangliosidosis (Leinekugel et al 1992), Gaucher (Gieselmann 2005), and Niemann-Pick type A and B diseases .…”

Section: Threshold Theorymentioning

confidence: 93%

Lysosomal Lipid Storage Diseases

Schulze

Sandhoff

2011

Cold Spring Harbor Perspectives in Biology

169

151

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“…Several methods have been used to quantify sulfatides, including TLC ( 19 ), HPLC ( 14,20 ), and, more recently, MS ( 4,13,15,(21)(22)(23)(24)(25). Here we describe a LC/MS/MS method to quantify sulfatides and their molecular species over a wide range of concentrations in normal and diseased tissues, plasma, and urine.…”

Section: Extraction Of Sulfatides From Plasma and Tissue Homogenatesmentioning

confidence: 99%

Quantification of sulfatides and lysosulfatides in tissues and body fluids by liquid chromatography-tandem mass spectrometry

Mirzaian

Kramer²,

Poorthuis

2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org high concentrations are found in selected organs, including kidney, colon, pancreas, and gall bladder. Increased concentrations of sulfatides have been reported in renal cell carcinoma, adenocarcinoma of colon and lung, and ovarian cancer ( 2, 4 ). Sulfatides have been proposed to play a role as ion barriers to osmotic stress and as counterions of ammonium in the renal adaptation to chronic metabolic acidosis ( 5,6 ) Sulfatides are synthesized from their precursor galactosylceramide in the Golgi apparatus by 3-O-sulfation of the galactose residue by the enzyme 3 ′ -phosphoadenosine-5 ′ -phosphosulfate: cerebroside sulfotransferase (CST) (EC2.8.2.11). Galactosylceramide is synthesized in the endoplasmic reticulum from ceramides and UDP-galactose by the enzyme UDP-galactose:ceramide galactosyltransferase (CGT) (EC 2.4.1.45) and is then transported to the Golgi apparatus prior to sulfation to sulfatides. Sulfatides consist of many molecular species, with structures differing in acyl chain length and hydroxylation and sphingoid base. These sulfatide molecular species are cell and tissue specifi c, which may be explained by the cell-and tissuespecifi c expression of ceramide synthases and fatty acid 2-hydroxylase ( 1, 7 ). It is diffi cult to assign specifi c functions to the different molecular species of sulfatides, but sulfatides with C16:0 fatty acids were reported to be involved in the regulation of insulin secretion in rat pancreatic ␤ -cells ( 8 ), and elevated levels of C18:0 sulfatides have been implicated as a cause of audiogenic seizers in mice overexpressing CGT ( 9 ). There is also heterogeneity of the sphingoid base composition of sulfatides. Most of the Abstract Sulfatides are found in brain as components of myelin, oligodendrocytes, and neurons but are also present in various visceral tissues. Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder caused by a defi ciency of arylsulfatase A, leading to severe white matter disease due to the accumulation of sulfatides and lysosulfatides. To study the physiological role of sulfatides, accessible and sensitive quantitative methods are required. We developed a sensitive LC/MS/MS method to quantify total sulfatide and lysosulfatide content as well as individual molecular species in urine and plasma from MLD patients and plasma and tissues from an MLD mouse model. Our results demonstrate that the method can quantify a wide range of sulfatide concentrations and can be used to quantify total sulfatide content and levels of individual molecular species of sulfatides in tissues, cells, and body fl uids. Even though plasma sulfatides and lysosulfatides would seem attractive candidate biomarkers that could possibly correlate with the severity of MLD and be of use to monitor the effects of therapeutic intervention, our results indicate that it is unlikely that the determination of these storage products in plasma will be useful in this respect. Sulfatides are anionic sulfoglycolipids main...

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Biochemical profiling to predict disease severity in metachromatic leukodystrophy

Cited by 23 publications

References 24 publications

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

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

Lysosomal Lipid Storage Diseases

Quantification of sulfatides and lysosulfatides in tissues and body fluids by liquid chromatography-tandem mass spectrometry

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