Abstract:
:750 MHz 1H NMR spectroscopy has been used to characterise in detail the abnormal low molecular weight metabolites of urine from two patients with inborn errors of metabolism. One case of the rare condition 2-hydroxyglutaric aciduria has been examined. There is at present no rapid routine method to detect this genetic defect, although NMR spectroscopy of urine is shown to provide a distinctive pattern of resonances. Assignment of a number of prominent urinary metabolites not normally seen in control urine could be made on the basis of their known NMR spectral parameters including the diagnostic marker 2-hydroxyglutaric acid, which served to confirm the condition. In addition, 750 MHz 1H NMR spectroscopy has been used to characterise further the abnormal metabolic profile of urine from a patient with maple syrup urine disease. This abnormality arises from a defect in branched chain keto-acid decarboxylase activity and results in a build up in the urine of high levels of branched chain oxo- and hydroxy-acids resulting from altered metabolism of the branched chain amino acids, valine, leucine and isoleucine. A number of previously undetected abnormal metabolites have been identified through the use of one-dimensional and two-dimensional J-resolved and COSY 750 MHz 1H NMR spectroscopy, including ethanol, 2-hydroxy-isovalerate, 2,3-dihydroxy-valerate, 2-oxo-3-methyl-n-valerate and 2-oxo-isocaproate. NMR spectroscopy of urine, particularly when combined with automatic data reduction and computer pattern recognition using a combination of biochemical markers, promises to provide an efficient alternative to other techniques for the diagnosis of inborn errors of metabolism.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Holmes E,Foxall PJ,Spraul M,Farrant RD,Nicholson JK,Lindon JCdoi
10.1016/s0731-7085(97)00066-6subject
Has Abstractpub_date
1997-07-01 00:00:00pages
1647-59issue
11eissn
0731-7085issn
1873-264Xpii
S0731708597000666journal_volume
15pub_type
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