Heparin co-factor II Thrombin complex as a biomarker for mucopolysaccharidosis: Indian experience (original) (raw)
Related papers
Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis
Molecular genetics and metabolism, 2018
To explore the correlation between glycosaminoglycan (GAG) levels and mucopolysaccharidosis (MPS) type, we have evaluated the GAG levels in blood of MPS II, III, IVA, and IVB and urine of MPS IVA, IVB, and VI by tandem mass spectrometry. Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS; mono-sulfated KS, di-sulfated KS), and the ratio of di-sulfated KS in total KS were measured. Patients with untreated MPS II had higher levels of DS and HS in blood while untreated MPS III had higher levels of HS in blood than age-matched controls. Untreated MPS IVA had higher levels of KS in blood and urine than age-matched controls. The ratio of blood di-sulfated KS/total KS in untreated MPS IVA was constant and higher than that in controls for children up to 10 years of age. The ratio of urine di-sulfated KS/total KS in untreated MPS IVA was also higher than that in age-matched controls, but the ratio in untreated MPS IVB was lower than controls. ERT reduced blood DS and HS in MPS ...
Iranian journal of child neurology, 2014
The first line-screening test for mucopolysaccharidosis is based on measurement of urinary glycosaminoglycans. The most reliable test for measurement of urine glycosaminoglycans is the 1,9-dimethyleneblue colorimetric assay. Biological markers are affected by ethnical factors, for this reason, the World Health Organization recommends that the diagnostic test characteristics should be used to determine results for different populations. This study determines the diagnostic value of 1,9-dimethyleneblue tests for diagnosis of mucopolysaccharidosis type I patients in Iran. In addition to routine urine analysis, the qualitative and quantitative measurements of urine glucosaminoglycans were performed with the Berry spot test and 1,9-dimethyleneblue assay. Diagnostic values of the tests were determined using the ROC curve. Urine total glycosaminoglycans were significantly higher in male subjects than in female subjects. Glycosaminoglycan concentration was markedly decreased in specimens wi...
The relationships between urinary glycosaminoglycan levels and phenotypes of mucopolysaccharidoses
Molecular Genetics & Genomic Medicine
Background: The aim of this study was to use the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method to quantitate levels of three urinary glycosaminoglycans (GAGs; dermatan sulfate [DS], heparan sulfate [HS], and keratan sulfate [KS]) to help make a correct diagnosis of mucopolysaccharidosis (MPS). Methods: We analyzed the relationships between phenotypes and levels of urinary GAGs of 79 patients with different types of MPS. Results: The patients with mental retardation (n = 21) had significantly higher levels of HS than those without mental retardation (n = 58; 328.8 vs. 3.2 μg/ml, p < 0.001). The DS levels in the patients with hernia, hepatosplenomegaly, claw hands, coarse face, valvular heart disease, and joint stiffness were higher than those without. Twenty patients received enzyme replacement therapy (ERT) for 1-12.3 years. After ERT, the KS level decreased by 90% in the patients with MPS IVA compared to a 31% decrease in the change of dimethylmethylene blue (DMB) ratio. The DS level decreased by 79% after ERT in the patients with MPS VI compared to a 66% decrease in the change of DMB ratio. Conclusions: The measurement of GAG fractionation biomarkers using the LC-MS/MS method is a more sensitive and reliable tool than the DMB ratio for MPS Abbreviations: 2-D EP, two-dimensional electrophoresis; CS, chondroitin sulfate; DMB, dimethylmethylene blue; DS, dermatan sulfate; ERT, enzyme replacement therapy; GAGs, glycosaminoglycans; HS, heparan sulfate; KS, keratan sulfate; LC-MS/MS, liquid chromatography/tandem mass spectrometry; MPS, mucopolysaccharidosis.
Scientific Reports
Mucopolysaccharidosis (MPS) is caused by the deficiency of a specific hydrolytic enzyme that catalyzes the step-wise degradation of glycosaminoglycans (GAGs). In this study, we propose an empirical method to calculate levels of GAG-derived disaccharides based on the quantity (peak areas) of chondroitin sulfate (Cs) with the aim of making a diagnosis of Mps more accurate and reducing the occurrence of false positive and false negative results. In this study, levels of urinary GAG-derived disaccharides were measured in 67 patients with different types of MPS and 165 controls without MPS using a tandem mass spectrometry assay. Two different methods of reporting GAG-derived disaccharides were assessed; normalization to urinary Cs (in μg/mL), and normalization to μg/ mg creatinine. Cs-normalization yielded more consistent values than creatinine-normalization. In particular, levels of urinary dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) significantly varied because of changes in urine creatinine levels, which were proportional to age but inversely proportional to DS, HS, and KS measurements. Using CS-normalization revealed the actual status of DS, HS, and KS without the influence of factors such as age, urine creatinine, and other physiological conditions. It could discriminate between the patients with Mps and controls without MPS, and also to evaluate changes in GAG levels pre-and post-enzyme replacement therapy. Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders (LSDs) caused by deficiency in one specific enzyme that catalyzes the stepwise degradation of glycosaminoglycans (GAGs). Depending on the type of MPS, this deficiency leads to excessive lysosomal storage of either chondroitin sulfate (CS), dermatan sulfate (DS), heparin sulfate (HS), or keratan sulfate (KS) and results in devastating manifestations such as coarse facial features, developmental delay and decline, gibbus, hepatosplenomegaly, cardiac valve disease, umbilical and inguinal hernias, joint deformity with a restricted range of motion, airway dysfunction with complications, sleep apnea, recurrent otitis media, and premature death 1-5. The clinical manifestations of MPS are chronic and progressive, and the initial onset of clinical signs and symptoms of MPS emerge between the ages of 18 months and 4 years, depending on disease severity 6-8. Enzyme replacement therapy (ERT) is widely used and available for MPS I, MPS II, MPS IVA and MPS VI 5,9-14 , and trials are currently ongoing for MPS IIIB. Achieving optimal benefits from ERT requires commencing treatment before the onset of irreversible clinical presentations 5,15,16 .
Mucopolysaccharidosis III: Molecular basis and treatment
Pediatric Endocrinology Diabetes and Metabolism
Mucopolysaccharidoses (MPSs) are known as rare genetic diseases which are caused by mutation in the enzyme heparin sulfate, which normally leads to degradation and accumulation of glycosaminoglycans in the cells. There are 11 types of MPSs, whereby neuropathy may occur in seven of them (MPS I, II, IIIA, IIIB, IIIC, IIID and VII). Accumulation of degraded heparin sulfate in lysosomes causes cellular dysfunction and malfunction of several organs. However, the exact molecular mechanism how protein degradation and storage leads to cellular dysfunction is not understood, yet. Nonetheless, several genetic and biochemical methods for diagnosis of MPSs are available nowadays. Here we provide an overview on known molecular basis of MPS in general, including enzyme defects and symptoms of MPS; however, the main focus is on MPS type III together with potential and perspective therapy-options.
Clinical and biochemical studies in mucopolysaccharidosis type II carriers
Journal of Inherited Metabolic Disease, 2009
The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for noncarriers; there was, however, an overlap between carriers_ and non-carriers_ values. Our data suggests
120: Glycosaminoglycans as Anticoagulants in Mucopolysaccharidosis Type I (MPS I)
Biology of Blood and Marrow Transplantation, 2008
on median donor graft mDC (0.81 Â 10 6 /kg recipient weight), or pDC (0.67 Â 10 6 /kg), or monocyte (6.6 Â 10 6 /kg) counts. No correlation was observed between acute and chronic GVHD as well as relapse and APC counts. However, the mortality rate was significantly higher in patients who received a greater dose of monocytes (24/41 vs 11/41) (p 5 0.003), with a trend for a more elevated TRM (15/41 vs 8/41) (p 5 0.08), as compared to patients who received a lower dose of monocytes. mDC and pDC counts did not correlate with survival after transplant. In univariate analysis, TRM correlated with advanced disease (p 5 0.03), age (p 5 0.039) and graft monocyte and T cell counts (both p 5 0.03), whereas overall mortality correlated with advanced disease (p\0.0001) and graft monocyte counts (p 5 0.02). In multivariate analysis, monocyte counts correlated with both TRM (p 5 0.06) and overall mortality (p 5 0.01). Conclusion: Donor CD141 cell dose in bone marrow grafts independently correlates with mortality following allogeneic transplantation suggesting a possible role of donor mature accessory cells in the regulation of post-transplant immunologic events.
Diagnosis of mucopolysaccharidoses: how to avoid false positives and false negatives
Indian journal of pediatrics, 2004
This paper advocates a complete procedure, which includes both quantitative and qualitative analysis of urinary GAGs in the diagnosis of MPS in a clinically suspected population. Urine samples from 219 clinically suspected mucopolysaccharidoses (MPS) patients and 91 controls were analysed using a combination of methods. Quantitation of isolated urinary glycosaminoglycans (GAGs) were carried out using acid alcian blue complex formation method and qualitative urinary GAG analysis by multisolvent sequential thin layer chromatography Of the 219 patients analysed, 131 were confirmed to be suffering from MPS. Quantitation of urinary GAGs alone would have missed 60 low GAG excreting MPS patients and misdiagnosed 26 high GAG excreting nonMPS as MPS patients. Further qualitative analysis and enzyme estimation were needed to identify these 60 low GAG excreting MPS patients and 26 high GAG excreting non MPS patients. These results emphasize that quantitation of urinary GAGs alone cannot diagno...