Pre- and post-dialysis quantitative dosage of thymidine in urine and plasma of a MNGIE patient by using HPLC-ESI-MS/MS

• Published in: Journal of mass spectrometry. Vol. 41; no. 5; pp. 586 - 592
• Main Authors: la Marca, G., Malvagia, S., Casetta, B., Pasquini, E., Pela, I., Hirano, M., Donati, M. A., Zammarchi, E.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.2006; Wiley
• Subjects: Adult; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; dialysis; Fatal Outcome; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Metabolic diseases; Mitochondrial Encephalomyopathies - blood; Mitochondrial Encephalomyopathies - therapy; Mitochondrial Encephalomyopathies - urine; MNGIE; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; pyrimidine; Renal Dialysis; Spectrometry, Mass, Electrospray Ionization - methods; tandem mass spectrometry; thymidine; Thymidine - analysis; Thymidine - blood; Thymidine - urine; Thymidine Phosphorylase - deficiency; Biological fluid; Chemical analysis; MNGIE; HPLC chromatography; Thymidine; Enzymopathy; Mitochondrial disorder; Electrospray; Blood; Blood plasma; tandem mass spectrometry; Clinical biology; Diagnosis; Pyrimidine nucleoside; Quantitative analysis; Human; Urine; Nervous system diseases; Coupled method; Metabolic diseases; Patient; Genetic disease; Striated muscle disease; Mass spectrometry MS/MS; Central nervous system disease; Mitochondrial encephalopathy; Digestive diseases; Dialysis; Mitochondrial myopathy; pyrimidine
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/jms.1013

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. The disease is due to a thymidine phosphorylase defect. This enzyme catalyses the phosphorolysis of thymidine to thymine and deoxyribose 1‐phosphate. For this reason, increased levels of thymidine in plasma and urine are found in MNGIE patients. Haemodialysis can reduce circulating plasma thymidine levels and can be beneficial in some MNGIE patients. We developed a fast analytical method based on HPLC‐ESI‐MS/MS capable of identifying pyrimidine nucleotides (thymine, cytosine, uracil) and nucleosides (thymidine, citidine, uridine) in plasma and urine after direct dilution of the samples without pre‐treatment. In the patient studied, we observed a significant reduction of plasmatic and urinary thymidine levels during and after dialysis. However, we noted a progressive reduction of the initial thymidine level after some dialytic trials. This method will be useful not only for thymidine level follow‐up during dialysis in MNGIE patients but also for the improvement of the diagnosis or diagnostic suspect in other pyrimidine defects such as dihydropyrimidine dehydrogenase deficiency, dihydropyrimidinase deficiency and ureidopropionase deficiency. Copyright © 2006 John Wiley & Sons, Ltd.