1H-NMR Spectroscopy of Body Fluids: Inborn Errors of Purine and Pyrimidine Metabolism

Abstract

Background: The diagnosis of inborn errors of purine and pyrimidine metabolism is often difficult. We examined the potential of 1H-NMR as a tool in evaluation of patients with these disorders. Methods: We performed 1H-NMR spectroscopy on 500 and 600 MHz instruments with a standardized sample volume of 500 μL. We studied body fluids from 25 patients with nine inborn errors of purine and pyrimidine metabolism. Results: Characteristic abnormalities could be demonstrated in the 1H-NMR spectra of urine samples of all patients with diseases in the pyrimidine metabolism. In most urine samples from patients with defects in the purine metabolism, the 1H-NMR spectrum pointed to the specific diagnosis in a straightforward manner. The only exception was a urine from a case of adenine phosphoribosyl transferase deficiency in which the accumulating metabolite, 2,8-dihydroxyadenine, was not seen under the operating conditions used. Similarly, uric acid was not measured. We provide the 1H-NMR spectral characteristics of many intermediates in purine and pyrimidine metabolism that may be relevant for future studies in this field. Conclusion: The overview of metabolism that is provided by 1H-NMR spectroscopy makes the technique a valuable screening tool in the detection of inborn errors of purine and pyrimidine metabolism.

Direct and Real-Time Quantification of Tenofovir Release from pH-Sensitive Microparticles into Simulated Biological Fluids Using 1H Nuclear Magnetic Resonance

“…20,21,26 However, the levels of LOD and LOQ values found in this study are comparable with other published applications of NMR in the field of pharmaceutical research, 27,28 including those using a higher magnetic field. 29,30 Although LOD and LOQ values may be lower using other methods (i.e., the HPLC method), the focus of this study is to quantify the amount of TNF release in biological fluid simulant rather than determine its aqueous solubility limit. Therefore, it is reasonably speculated that NMRderived LOD and LOQ values may frequently be sufficient to establish in vitro drug release in the approximate microgram quantities that are typical of drug formulations, as in this study.…”

Metabolic characterisation of plasma in juveniles with glycogen storage disease type 1a (GSD1a) by high‐resolution 1H NMR spectroscopy

“…Inborn errors of metabolism are a class of diseases where NMR spectroscopy has been shown to be particularly useful, as alterations in a wide range of metabolites can be detected simultaneously without making a priori assumptions about the metabolic processes involved, thus allowing the identification of possible biomarkers. Indeed, NMR has not only shown its diagnostic value for known errors of metabolism (3)(4)(5)(6)(7)(8), but has also led to the discovery of new inborn errors (9)(10)(11).…”

Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high–pressure liquid chromatography–electrospray ionization tandem mass spectrometry

“…In 2% of our patients we found moderate elevations of DHU (30-70 µmol/mmol creatinine) and DHT (4-16 µmol/mmol creatinine) compared to reference values in healthy controls (see Table 4). It is interesting to note that Kuhara and colleagues (2003) also found only slightly elevated excretion of DHU and DHT in patients with dihydropyrimidinase deficiency, whereas other groups reported much higher levels in those patients (Assmann et al 1997;van Kuilenburg et al 1998;Wevers et al 1999). The explanation for this observation is still unknown, but systematic mutational screening for functionally relevant genetic variants in the dihydropyrimidinase gene may bring more insight in the future.…”