Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long‐term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans

Ru, Minke H. de; Tol, Linda van der; Vlies, Naomi van; Bigger, Brian; Hollak, Carla E. M.; IJlst, Lodewijk; Kulik, Wim; Lenthe, Henk van; Saif, M; Wagemans, Tom; Wal, Willem M. van der; Wanders, Ronald J. A.; Wijburg, Frits A.

doi:10.1007/s10545-012-9538-2

Cited by 47 publications

(57 citation statements)

References 24 publications

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“…5) in patients with respiratory failure may not only reflect ongoing glycocalyx degradation but also could indicate an impairment of glycosaminoglycan clearance. Although hepatic or renal dysfunction may delay clearance of circulating glycosaminoglycans (32)(33)(34), the relative homogeneity of indices of renal function (blood urea nitrogen, creatinine) and hepatic function (bilirubin, international normalized ratio) across groups (Table 1) suggests that the observed glycosaminoglycan signatures are not the primary consequence of aberrant liver or kidney clearance. Our data, however, cannot exclude subtle abnormalities in renal and/or hepatic function that are not captured by these common indices of organ function.…”

Section: Discussionmentioning

confidence: 99%

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

Schmidt

et al. 2014

Journal of Biological Chemistry

131

137

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Background: Endothelial glycocalyx degradation contributes to the pathogenesis of critical illness. Results: Mechanically ventilated subjects exhibited plasma glycocalyx breakdown signatures (glycosaminoglycan fragments) characteristic of direct versus indirect etiologies of respiratory failure. Conclusion: Circulating glycosaminoglycans provide insight into respiratory failure pathophysiology. Significance: This is the first study to characterize circulating glycosaminoglycans during critical illness, offering insight into the mechanisms underlying respiratory failure.

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Section: Discussionmentioning

confidence: 99%

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

Schmidt

et al. 2014

Journal of Biological Chemistry

131

137

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“…The LC-MS/MS method not only shows sensitivity and specificity for detecting all subtypes of MPS but also is able to monitor therapeutic efficacy in MPS patients and animal models [15,63,[98][99][100][101][102][103]. This new method has an advantage of being both GAG-specific and quantitative.…”

Section: Tandem Mass Spectrometry (Ms/ms)-inmentioning

confidence: 99%

Newborn screening and diagnosis of mucopolysaccharidoses

Tomatsu

Shimada

Montaño

et al. 2014

Molecular Genetics and Metabolism

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Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical. We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5-99.4%; positive predictive value, 54.5-75%; false positive rate, 0.62-1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false

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“…GAG levels in mouse plasma, liver, and humerus homogenates were determined using HPLC-MS/MS, as described previously (de Ru et al 2013), with one modification for tissue samples: 12.5 mg protein of liver or humerus homogenates were used. Genistein supplementation did not alter HS or DS disaccharide composition; therefore, only values of the most abundant HS derived disaccharide D0A0 and DS derived disaccharide D0a4 are given.…”

Section: Gag Analysismentioning

confidence: 99%

Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model

et al. 2015

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by diminished degradation of the glycosaminoglycans heparan sulfate (HS) and dermatan sulfate (DS). Patients present with a variety of symptoms, including severe skeletal disease. Current therapeutic strategies have only limited effects on bone disease. The isoflavone genistein has been studied as a potential therapy for the mucopolysaccharidoses because of its putative ability to inhibit GAG synthesis and subsequent accumulation. Cell, animal, and clinical studies, however, showed variable outcomes. To determine the effects of genistein on MPS I-related bone disease, wild-type (WT) and MPS I mice were fed a genistein-supplemented diet (corresponding to a dose of approximately 160 mg/kg/day) for 8 weeks. HS and DS levels in bone and plasma remained unchanged after genistein supplementation, while liver HS levels were decreased in genistein-fed MPS I mice as compared to untreated MPS I mice. Unexpectedly, genistein-fed mice exhibited significantly decreased body length and femur length. In addition, 60% of genistein-fed MPS I mice developed a scrotal hernia and/or scrotal hydrocele, manifestations ,which were absent in WT or untreated MPS I mice. In contrast to studies in MPS III mice, our study in MPS I mice demonstraes no beneficial but even potential adverse effects of genistein supplementation. Our results urge for a cautious approach on the use of genistein, at least in patients with MPS I.

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Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long‐term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans

Cited by 47 publications

References 24 publications

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

Newborn screening and diagnosis of mucopolysaccharidoses

Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model

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