Abstract
The diagnosis of the majority of the known inherited defects of purine and pyrimidine metabolism can be achieved by analysing urinary excretion profiles. A quantitative measurement of the urinary uric acid/creatinine ratio should be the first approach for purine defects. The general screening system involves separation of the bases and nucleosides by reversed-phase high-performance liquid chromatography and multiwavelength UV detection. The catabolic defects of pyrimidine degradation can be diagnosed by gas chromatography - mass spectrometry as used for organic acids. For the detection of adenylosuccinase deficiency, several simple but effective thin-layer chromatographic methods are available.
Techniques such as liquid chromatography - mass spectrometry, direct nega-tive-ion fast-atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy give promising results, but are not yet being used on a large scale. Patients should keep to a simple diet and preferably be free of medication in order to allow a reliable interpretation of the analytical data.
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REFERENCES
Berger R, Stoker-de Vries SA, Wadman SK, et al (1984) Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. Clin Chim Acta 141: 227–234.
Berglund G, Greter J, Lindstedt S, Steen G, Waldenström J, Wass U (1979) Urinary excretion of thymine and uracil in a two-year-old child with a malignant tumor of the brain. Clin Chem 25: 1325–1328.
Brusilow S, Hauser E (1989) A simple method of measurement of orotic acid and orotidine. J Chromatogr 493: 388–391.
Chantin C, Bonin B, Boulieu R, Bory C (1996) Liquid-chromatographic study of purine metabolism abnormalities in purine nucleoside phosphorylase deficiency. Clin Chem 42: 326–328.
Clayton PT (1996) Disorders of bile acid synthesis. In Blau N, Duran M, Blaskovics ME, eds. Physician's Guide to the Laboratory Diagnosis of Metabolic Disease. London: Chapman & Hall Medical, 453–465.
De Bree PK, Wadman SK, Duran M, Fabery de Jonge H (1986) Diagnosis of inherited adenylosuccinase deficiency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. Clin Chim Acta 156: 279–288.
Dent CE, Philpot GR (1954) Xanthinuria, and inborn error (or deviation) of metabolism. Lancet 1; 182–185.
Duran M, Rovers P, de Bree PK, et al (1990) Dihydropyrimidinuria. Lancet 336: 817–818.
Duran M, Dorland L, Wadman SK, Berger R (1994) Group tests for selective screening of inborn errors of metabolism. Eur J Pediatr 153(supplement 1): S27–S32.
Henderson MJ, Ward K, Simmonds HA, Duley JA, Davies PM (1993) Dihydropyrimidinase deficiency presenting in infancy with severe developmental delay. J Inher Metab Dis 16: 574–576.
Hoffmann GF (1996) Organic acids. In Blau N, Duran M, Blaskovics ME, eds. Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases. London: Chapman & Hall Medical, 33–49.
Jaeken J, Van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2: 1058–1061.
Jaeken J, Cock P de, Duran M, et al (1988) Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. Eur J Pediatr 148: 126–131.
Maddocks J, Reed T (1989) Urine test for adenylosuccinase deficiency in autistic children. Lancet 1: 158–159.
Rijksen G, Kuis W, Wadman SK, et al (1987) A new case of purine nucleoside phosphorylase deficiency: enzymological, clinical and immunological characteristics. Pediatr Res 21: 137–141.
Simmonds HA, Duley JA, Davies PM (1991) Analysis of purines and pyrimidines in blood, urine, and other physiological fluids. In Hommes FA, ed. Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual. New York: Wiley-Liss, 397–424.
Simmonds HA, Duley JA, Fairbanks LD, McBride MB (1997) When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications. J Inher Metab Dis 20: 214–226.
Van den Berghe G, Vincent MF, Jaeken J (1997) Inborn errors of the purine nucleotide cycle: Adenylosuccinase deficiency. J Inher Metab Dis 20: 193–202.
van Gennip AH, Grift J, Bree-Blom EJ van, Ketting D, Wadman SK (1979) Urinary excretion of methylated purines in man and in the rat after the administration of theophylline. J Chromatogr 163: 351–362.
Wadman SK, Fabery de Jonge H, Bree PK de (1969) Rapid, high-resolution, two-dimensional amino acid chromatography on micro-scale chromatograms. Clin Chim Acta 25: 87–90.
Wadman SK, Duran M, Beemer FA, et al (1983) Absence of hepatic molybdenum cofactor — an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase. J Inher Metab Dis 6(supplement 1): 78–83.
Wevers RA, Abreu RA de, Engelke U, Heerschap A, Gennip AH van (1996) 1H-NMR spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism. J Inher Metab Dis 19(supplement 1): 3 (abstract).
Wilcox WD (1996) Abnormal serum uric acid levels in children. J Pediatr 128: 731–741.
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Duran, M., Dorland, L., Meuleman, E.E.E. et al. Inherited defects of purine and pyrimidine metabolism: Laboratory methods for diagnosis. J Inherit Metab Dis 20, 227–236 (1997). https://doi.org/10.1023/A:1005360907238
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DOI: https://doi.org/10.1023/A:1005360907238