Urinary Glycosaminoglycan Excretion in Healthy Subjects and in Patients with Mucopolysaccharidoses

Gallegos‐Arreola, Martha Patricia; Machorro-Lazo, Maria-Victoria; Flores-Martínez, Silvia Esperanza; Zúñiga‐González, Guillermo Moisés; Figuera, Luis E.; González-Noriega, Alfonso; Sánchez‐Corona, José

doi:10.1016/s0188-4409(00)00104-1

Cited by 52 publications

(33 citation statements)

References 4 publications

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“…The measurement of total GAG excretion in urine is widely used as a biomarker for MPS [65][66][67]. Urine GAG analysis is a useful initial screening test for MPS and may be also helpful for monitoring treatment efficacy.…”

Section: Total Urine Gag Assaymentioning

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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Section: Total Urine Gag Assaymentioning

confidence: 99%

Newborn screening and diagnosis of mucopolysaccharidoses

Tomatsu

Shimada

Montaño

et al. 2014

Molecular Genetics and Metabolism

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“…This assumption may be extended to the hypothesis that GAG in the urine may reflect the turnover of GAG in the glomerulus. Urinary GAG has been suggested as a clinical marker in various diseases, including lupus nephritis [8, 9], urinary bladder damage and bladder tumors [10, 11, 12, 13], mucopolysaccharidoses [14], renal amyloidosis [15], primary glomerulonephritis in experimental animal models and humans [5, 16, 17], proteolytic injury of endothelial and basement membranes which induce capillary leaks in meningococcal septicemia [18], chronic pyelonephritis [19], chronic obstructive pulmonary disease [20], and diabetic nephropathy [21, 22, 23, 24, 25]. An association between heparan sulfate proteoglycan in urine and proteinuria has been reported after renal transplantation [26].…”

Section: Introductionmentioning

confidence: 99%

Isolation, Identification, and Quantitation of Urinary Glycosaminoglycans

Lee

Kim²,

Whang³

et al. 2003

Am J Nephrol

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Background: Substantial amounts of glycosaminoglycans (GAGs) are present in the urine of healthy individuals, but the concentration in the serum is very low. This finding suggests that urinary GAGs come from the glomerulus and may reflect the turnover of GAGs in the glomerulus. Hypothesis: However, little is known about the physiologic regulation of the urinary GAGs in humans, and so investigations are needed to evaluate the effects of age and sex on urinary GAGs in normal individuals. Methods: Eighty-seven healthy subjects were included in this study. Urinary GAGs were isolated and quantified at the nanogram level by combined azure A-silver staining in agarose gels. Results: The level of urinary GAGs peaked at 10–19 years in both sexes. The proportion of chondroitin sulfate decreased with age, but the proportion of heparan sulfate increased with age. Conclusion: The total amount of GAGs and the proportions of chondroitin sulfate, heparan sulfate, and dermatan sulfate appear to change with age. Therefore, investigations in which urinary GAG is used as a parameter of glomerular GAG turnover should ensure that control groups are precisely matched for age. Changes in the proportions of each GAG may be more informative than their absolute levels.

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“…On the basis of our findings, we suggest that agarose gel electrophoresis using a commercially available gel matrix could be used for neonatal MPS screening through analysis of urinary GAGs. The electrophoretic profile of GAGs separated by electrophoresis has been applied as a screening tool to identify MPS, with satisfactory results (De Lima, Baccarin, Michelacci, 2007;Gallegos-Arreola et al, 2000;Piraud et al, 1993). Electrophoretic analysis can also rule out suspicion of MPS, as our results indicate that healthy individuals do not accumulate GAGs through visible bands.…”

Section: Discussionmentioning

confidence: 64%

Use of a commercial agarose gel for analysis of urinary glycosaminoglycans in mucopolysaccharidoses

Breier

Cé

Coelho

2016

Braz. J. Pharm. Sci.

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Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by deficiency of enzymes that degrade glycosaminoglycans (GAGs). Urinary excretion of GAGs is a common feature of MPS, and is considered their major biomarker. We aimed to adapt the GAG electrophoresis method to a commercial agarose gel which would be able to separate urinary GAGs in a simpler way with good sensitivity and reproducibility. Urine samples from patients previously diagnosed with MPS I, IV, and VI were used as electrophoretic standards. Samples from patients on enzyme replacement therapy (ERT) were also assessed. Commercial agarose gel electrophoresis was effective, showing proper definition and separation of GAG bands. Detection sensitivity exceeded 0.1 µg and band reproducibility were consistent. GAG bands quantified in urine samples from patients on ERT correlated very strongly (correlation coefficient = 0.98) with total GAG concentrations. This application of gel electrophoresis demonstrates the possibility of monitoring patients with MPS treated with ERT by analyzing separately the GAGs excreted in urine. We suggest this process should be applied to MPS screening as well as to follow-up of patients on treatment.Uniterms: Mucopolysaccharidoses/tests/treatment. Electrophoresis/monitoring method. Glycosaminoglycans/use.

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Urinary Glycosaminoglycan Excretion in Healthy Subjects and in Patients with Mucopolysaccharidoses

Cited by 52 publications

References 4 publications

Newborn screening and diagnosis of mucopolysaccharidoses

Newborn screening and diagnosis of mucopolysaccharidoses

Isolation, Identification, and Quantitation of Urinary Glycosaminoglycans

Use of a commercial agarose gel for analysis of urinary glycosaminoglycans in mucopolysaccharidoses

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