Diagnostic test for mucopolysaccharidosis. I. Direct method for quantifying excessive urinary glycosaminoglycan excretion.

Whitley, Chester B.; Ridnour, M. D.; Draper, Ken; Dutton, Charyl M.; Neglia, Joseph P.

doi:10.1093/clinchem/35.3.374

Cited by 200 publications

(92 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…U r i n a r yG A G sw e r em e a s u r e di nc o m p a r i s o nw i t hb l o o d and urine DS and HS values using dimethyl-methylene blue (DMB), as described previously (Whitley et al 1989) .C r e a t i n i n ew a sm e a s u r e db ym i x i n g1 0μlo fa tenfold-diluted urine sample with 50 μl saturated picric acid (Sigma-Aldrich, St. Louis, MO, USA) and 50 μl 0.2 M sodium hydroxide (NaOH). Absorbance at 490 nm was read after 20 min and compared with the standard.…”

Section: Measurement Of Urinary Gagsmentioning

confidence: 99%

Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

Tomatsu

Montaño

Oguma

et al. 2010

J of Inher Metab Disea

View full text Add to dashboard Cite

Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by deficiency of alpha-L-iduronidase leading to accumulation of its catabolic substrates, dermatan sulfate (DS) and heparan sulfate (HS), in lysosomes. This results in progressive multiorgan dysfunction and death in early childhood. The recent success of enzyme replacement therapy (ERT) for MPS I highlights the need for biomarkers that reflect response to such therapy. To determine which biochemical markers are better, we determined serum and urine DS and HS levels by liquid chromatography tandem mass spectrometry in ERT-treated MPS I patients. The group included one Hurler, 11 Hurler/Scheie, and two Scheie patients. Seven patients were treated from week 1, whereas the other seven were treated from week 26. Serum and urine DS (DeltaDi-4S/6S) and HS (DeltaDiHS-0S, DeltaDiHS-NS) were measured at baseline, week 26, and week 72. Serum DeltaDi-4S/6S, DeltaDiHS-0S, and DeltaDiHS-NS levels decreased by 72%, 56%, and 56%, respectively, from baseline at week 72. Urinary glycosaminoglycan level decreased by 61.2%, whereas urine DeltaDi-4S/6S, DeltaDiHS-0S, and DeltaDiHS-NS decreased by 66.8%, 71.8%, and 71%, respectively. Regardless of age and clinical severity, all patients showed marked decrease of DS and HS in blood and urine samples. We also evaluated serum DS and HS from dried blood-spot samples of three MPS I newborn patients, showing marked elevation of DS and HS levels compared with those in control newborns. In conclusion, blood and urine levels of DS and HS provide an intrinsic monitoring and screening tool for MPS I patients.

show abstract

Section: Measurement Of Urinary Gagsmentioning

confidence: 99%

Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

Tomatsu

Montaño

Oguma

et al. 2010

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Total GAG concentrations in urine samples were determined as previously described . Briefly, the method is based on spectrophotometric detection of metachromatic changes to the dye 1,9-dimethylmethylene blue (DMB) resulting from GAG binding [Whitley et al, 1989]. GAG concentrations were subsequently normalized to urinary creatinine concentrations, which were determined separately.…”

Section: Determination Of Urinary Gagsmentioning

confidence: 99%

Mutational analysis of 105 mucopolysaccharidosis type VI patients

et al. 2007

View full text Add to dashboard Cite

Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome) is a lysosomal storage disorder caused by mutations in the N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ARSB) gene. ARSB is a lysosomal enzyme involved in the degradation of the glycosaminoglycans (GAG) dermatan and chondroitin sulfate. ARSB mutations reduce enzyme function and GAG degradation, causing lysosomal storage and urinary excretion of these partially degraded substrates. Disease onset and rate of progression is variable, producing a spectrum of clinical presentation. In this study, 105 MPS VI patients-representing about 10% of the world MPS VI population-were studied for molecular genetic and biochemical parameters. Direct sequencing of patient genomic DNA was used to identify ARSB mutations. In total, 83 different disease-causing mutations were found, 62 of which were previously unknown. The novel sequence changes included: 38 missense mutations, five nonsense mutations, 11 deletions, one insertion, seven splice-site mutations, and four polymorphisms. ARSB mutant protein and residual activity were determined on fibroblast extracts for each patient. The identification of many novel mutations unique to individuals/their families highlighted the genetic heterogeneity of the disorder and provided an appropriate cohort to study the MPS VI phenotypic spectrum. This mutation analysis has identified a clear correlation between genotype and urinary GAG that can be used to predict clinical outcome.

show abstract

“…Urine was obtained every 1-6 weeks to determine the total GAG concentration, a surrogate for the extent of clearance of these compounds from lysosomes. Total GAG concentrations in urine samples were determined using a method based on spectrophotometric detection of metachromatic changes to the dye 1,9-dimethylmethylene blue that result from GAG binding [8]. Pharmacokinetic studies were performed at weeks 1, 2, 12, 24, 83, 84 and 96.…”

Section: Biochemical Studiesmentioning

confidence: 99%

Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux–Lamy syndrome): a phase I/II study

Harmatz¹,

Kramer²,

Hopwood³

et al. 2005

Acta Paediatrica

View full text Add to dashboard Cite

Aim: Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulphatase (ASB). Enzyme replacement therapy with recombinant human ASB (rhASB) has been studied in a randomized, double-blind, two-dose (0.2 and 1.0 mg/kg/week) phase I/II study (n=7) followed by an open-label single dose (1.0 mg/kg/week) extension study. We report the pharmacokinetic profile of rhASB and the impact of antibody development. Methods: Pharmacokinetic analysis was performed at weeks 1, 2, 12, 24, 83, 84 and 96. Infusions were administered over 4 hours using a ramp-up protocol. Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan (GAG) concentrations were determined. Results: The area under the plasma concentration-time curve (AUC 07t ) for the high-dose group increased from week 1 to week 2, but remained unchanged at weeks 12 and 24. A large difference in mean AUC 07t was observed between the low-and high-dose groups. Pharmacokinetic results at weeks 83, 84 and 96 were similar to those at week 24. Six patients developed antibodies to rhASB. One patient developed high antibody levels in combination with a high ASB concentration, while a second patient also developed high antibody levels with undetectable ASB concentrations. Antibodies from the second patient blocked detection of ASB. By week 72, antibody levels had decreased in all patients. The high-dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose (70% versus 55% at 24 weeks). Antibody levels did not appear to influence urinary GAG concentrations.Conclusion: Pharmacokinetic parameters appear to be independent of the duration of treatment and are not linear between the 0.2 and 1.0 mg/kg/week doses. Antibodies to rhASB develop in most patients, but their concentration decreases over time. Antibody formation may influence pharmacokinetic parameters during the early phases of treatment, although it appears to have limited impact on biochemical efficacy.

show abstract

Diagnostic test for mucopolysaccharidosis. I. Direct method for quantifying excessive urinary glycosaminoglycan excretion.

Cited by 200 publications

References 0 publications

Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

Mutational analysis of 105 mucopolysaccharidosis type VI patients

Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux–Lamy syndrome): a phase I/II study

Contact Info

Product

Resources

About