Determination of Oligosaccharides in Pompe Disease by Electrospray Ionization Tandem Mass Spectrometry
Open Access
- 1 January 2002
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Chemistry
- Vol. 48 (1) , 131-139
- https://doi.org/10.1093/clinchem/48.1.131
Abstract
Background: The development of therapies for lysosomal storage disorders has created a need for biochemical markers to monitor the efficacy of therapy and methods to quantify these markers in biologic samples. In Pompe disease, the concentration of a tetrasaccharide, consisting of four glucose residues, is reputedly increased in urine and plasma, but faster and more sensitive methods are required for the analysis of this, and other oligosaccharides, from biologic fluids. Methods: We optimized the derivatization of storage oligosaccharides with 1-phenyl-3-methyl-5-pyrazolone for the measurement, by electrospray ionization tandem mass spectrometry, of oligosaccharide concentrations in urine (n = 6), plasma (n = 11), and dried-blood spots (n = 17) from Pompe-affected individuals. Age-matched control samples of urine (n = 10), plasma (n = 28), and blood spots (n = 369) were also analyzed. Results: The mean tetrasaccharide concentration was increased in urine from infantile-onset (0.69–12 mmol/mol of creatinine) and adult-onset (0.22–3.0 mmol/mol of creatinine) Pompe individuals compared with age-matched controls. In plasma samples, an increased tetrasaccharide concentration was observed in some infantile patients (up to 22 μmol/L) compared with age-matched controls (mean, 2.2 μmol/L). The method developed was sensitive enough to determine oligosaccharide concentrations in a single 3-mm blood spot, but no differences were observed between blood spots from control and Pompe-affected individuals. Conclusions: Measurements of oligosaccharide concentrations in urine by this new method have potential application for the diagnosis and monitoring of patients with Pompe disease. Plasma analysis may have limited application for infantile patients, but analysis of blood spots does not discriminate between controls and affected individuals.Keywords
This publication has 26 references indexed in Scilit:
- Approach to Gene Therapy of Glycogenosis Type II (Pompe Disease)Molecular Genetics and Metabolism, 2000
- Modulation of disease severity in mice with targeted disruption of the acid α-glucosidase geneNeuromuscular Disorders, 2000
- Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counsellingEuropean Journal of Human Genetics, 1999
- Complete correction of acid α-glucosidase deficiency in Pompe disease fibroblasts in vitro, and lysosomally targeted expression in neonatal rat cardiac and skeletal muscleGene Therapy, 1998
- Clinical and metabolic correction of pompe disease by enzyme therapy in acid maltase-deficient quail.Journal of Clinical Investigation, 1998
- Retroviral Transfer of Acidα-Glucosidase cDNA to Enzyme-Deficient Myoblasts Results in Phenotypic Spread of the Genotypic Correction by Both Secretion and FusionHuman Gene Therapy, 1997
- A new non-equilibrium enzyme linked immunosorbent assay for a glycogen-derived urinary tetrasaccharideGlycoconjugate Journal, 1986
- Increased urinary excretion of a glucose‐containing tetrasaccharide in patients with duchenne muscular dystrophyFEBS Letters, 1979
- Quantitation of a urinary tetrasaccharide by gas chromatography and mass spectrometryJournal of Mass Spectrometry, 1976
- Increased Excretion of a Glucose‐Containing Tetrasaccharide in the Urine of a Patient with Glycogen Storage Disease Type II (Pompe's Disease)European Journal of Clinical Investigation, 1974