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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.

Background: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition.Methods: We used 1H NMR spectroscopy to study serum and urine from the patient.Results: The concentration of N,N-dimethylglycine (DMG) was increased ∼100-fold in the serum and ∼20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography–mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient.Conclusions: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.

Although spin-echo techniques are often used to obtain 1H-NMR spectra of serum or plasma samples, they do not provide reliable quantitative analyses of metabolites. We present a standardized procedure, optimized for sensitivity, for using single-pulse 1H-NMR spectroscopy to analyze deproteinized plasma. The detection limit for various metabolites ranges between 2 and 40 mumol/L. The method allows quantitative analysis of many compounds of interest in studies of inborn errors of metabolism, including betaine and dimethylglycine, which cannot be measured easily with other techniques. For lactate, tyrosine, threonine, and alanine, we obtained results that correlated well with those obtained by established techniques. We also present a library containing resonance positions of 38 compounds occurring in plasma samples in health and disease, including 14 as-yet-unidentified resonances. As an example of the diagnostic power of the technique we show a spectrum of a plasma sample from a patient with 5-oxoprolinuria (pyroglutamic aciduria; McKusick 266130), an enzymatic defect in glutathione biosynthesis.