Rapid ultraperformance liquid chromatography-tandem mass spectrometry assay for a characteristic glycogen-derived tetrasaccharide in Pompe disease and other glycogen storage diseases.
| Autor: | Sluiter W; Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands., van den Bosch JC, Goudriaan DA, van Gelder CM, de Vries JM, Huijmans JG, Reuser AJ, van der Ploeg AT, Ruijter GJ |
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| Jazyk: | angličtina |
| Zdroj: | Clinical chemistry [Clin Chem] 2012 Jul; Vol. 58 (7), pp. 1139-47. Date of Electronic Publication: 2012 May 23. |
| DOI: | 10.1373/clinchem.2011.178319 |
| Abstrakt: | Background: Urinary 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). Methods: Urine samples, diluted in 0.1% ammonium hydroxide containing the internal standard acarbose, were filtered, and the filtrate was analyzed by UPLC-MS/MS. Results: We 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. Conclusions: The 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: | MEDLINE |
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