Rapid Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry Assay for a Characteristic Glycogen-Derived Tetrasaccharide in Pompe Disease and Other Glycogen Storage Diseases
| Autor: | Arnold J. J. Reuser, Juna M. de Vries, J. G. M. Huijmans, Daphne A. Goudriaan, Wim Sluiter, Jeroen C. van den Bosch, Carin M. van Gelder, Ans T. van der Ploeg, George J. G. Ruijter |
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| Přispěvatelé: | Biochemistry, Clinical Genetics, Pediatrics, Neurology |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Spectrometry Mass Electrospray Ionization Adolescent Clinical Biochemistry Oligosaccharides macromolecular substances Urine Glycogen storage disease type III Glycogen Storage Disease Type III Glycogen Storage Disease Type IV Young Adult 03 medical and health sciences chemistry.chemical_compound Reference Values Tandem Mass Spectrometry Liquid chromatography–mass spectrometry Glycogen storage disease type II medicine Humans Glycogen storage disease Glycogen storage disease type IV Child Maltose Aged 030304 developmental biology 0303 health sciences Creatinine Chromatography Glycogen Glycogen Storage Disease Type II 030305 genetics & heredity Biochemistry (medical) Age Factors Infant Newborn Infant Middle Aged Glycogen Storage Disease medicine.disease 3. Good health carbohydrates (lipids) chemistry Child Preschool lipids (amino acids peptides and proteins) Chromatography Liquid |
| Zdroj: | Clinical Chemistry, 58(7), 1139-1147. American Association for Clinical Chemistry Inc. Clinical Chemistry; Vol 58 |
| ISSN: | 1530-8561 0009-9147 |
| DOI: | 10.1373/clinchem.2011.178319 |
| Popis: | BACKGROUNDUrinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) is increased in various clinical conditions associated with increased turnover or storage of glycogen, making Glc4 a potential biomarker for glycogen storage diseases (GSD). We developed an ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay to detect Glc4 in urine without interference of the Glc4 isomer maltotetraose (M4).METHODSUrine samples, diluted in 0.1% ammonium hydroxide containing the internal standard acarbose, were filtered, and the filtrate was analyzed by UPLC-MS/MS.RESULTSWe separated and quantified acarbose, M4, and Glc4 using the ion pairs m/z 644/161, 665/161, and 665/179, respectively. Response of Glc4 was linear up to 1500 μmol/L and the limit of quantification was 2.8 μmol/L. Intra- and interassay CVs were 18.0% and 18.4% (10 μmol/L Glc4), and 10.5% and 16.2% (200 μmol/L Glc4). Glc4 in control individuals (n = 116) decreased with increasing age from a mean value of 8.9 mmol/mol to 1.0 mmol/mol creatinine. M4 was present in 5% of urine samples. Mean Glc4 concentrations per age group in untreated patients with Pompe disease (GSD type II) (n = 66) were significantly higher, ranging from 39.4 to 10.3 mmol/mol creatinine (P < 0.001–0.005). The diagnostic sensitivity of Glc4 for GSD-II was 98.5% and the diagnostic specificity 92%. Urine Glc4 was also increased in GSD-III (8 of 9), GSD-IV (2 of 3) and GSD-IX (6 of 10) patients.CONCLUSIONSThe UPLC-MS/MS assay of Glc4 in urine was discriminative between Glc4 and M4 and confirmed the diagnosis in >98% of GSD-II cases. |
| Databáze: | OpenAIRE |
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