Summary
In addition to the previously reported abnormalities, urine extracts from three cases of succinic semialdehyde dehydrogenase deficiency have shown consistently increased amounts of 2,4-dihydroxybutric acid, and its lactone, and 3-hydroxypropionic acid, metabolites related to the α-oxidation of 4-hydroxybutyric acid.Threo- anderythro-4,5-dihydroxyhexanoic acids have also been identified for the first time and probably arise from the reaction of succinic semialdehyde with an intermediate in the pyruvate dehydrogenase pathway. Adipic acid excretion is also consistently raised, suggesting secondary interference with mitochondrial β-oxidation. The presence of these metabolites could be a source of diagnostic confusion.
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Bennett, M. J., Green, A., Pollitt, R. J. and Worthy, E. The routine investigation of urinary organic acids in selected paediatric patients: results over a 21/2-year period.Ann. Clin. Biochem. 21 (1984) 45–50
Cooper, R. H., Randle, P. J. and Denton, R. M. Regulation of heart muscle pyruvate dehydrogenase kinase.Biochem. J. 143 (1974) 625–641
Divry, P., Baltassat, P., Rolland, M. O., Cotte, J., Hermier, M., Duran, M. and Wadman, S. K. A new patient with 4-hydroxybutyric aciduria, a possible defect of 4-aminobutyrate metabolism.Clin. Chim. Acta 129 (1983) 303–309
Eccott, E. N. and Linstead, R. P. Investigation of the lower olefinic acids. 1. n-Hexenoic acids.J. Chem. Soc. (1929) 2153–2165
Fell, V., Lee, C. R. and Pollitt, R. J. The occurence of (S)-3,4-dihydroxybutyrate in human blood and urine.Biochem. Med. 13 (1975) 40–45
Gabriel, M. A., Jabara, H. and Al-Khalidi, U. A. S. Metabolism of acetoin in mammalian liver slices and extracts. Interconversion with butane-2,3-diol and biacetyl.Biochem. J. 124 (1971) 793–800
Haan, E. A., Brown, G. K., Mitchell, D. and Danks, D. M. Succinic semialdehyde dehydrogenase deficiency — a further case.J. Inher. Metab. Dis. 8 (1985) 99
Hommes, F. A., Bruins, A. P., Dajani-Wielaard, J. and Baarsma, R. 2,3-Dihydroxybutane: An unusual compound found in the gas chromatographic analysis of volatile compounds of urine.J. Clin. Chem. Biochem. 17 (1979) 97–99
Jakobs, C., Bojasch, M., Monch, E., Rating, D., Siemes, H. and Hanefeld, F. Urinary excretion of gamma-hydroxybutyric acid in a patient with neurological abnormalities. The probability of a new inborn error of metabolism.Clin. Chim. Acta 111 (1981) 169–178
Juni, E. and Heym, G. A. Acyloin condensation reactions of pyruvic oxidase.J. Biol. Chem. 218 (1956) 365–378
Lee, C. R. Evidence for the β-oxidation of orally administered 4-hydroxybutyrate in humans.Biochem. Med. 17 (1977) 284–291
Lindblad, B. and Steen, G. Identification of 4,6-dioxoheptanoic acid (succinylacetone), 3,5-dioxooctanedioic acid (succinylacetoacetate) and 4-oxo-6-hydroxyheptaonic acid in the urine from patients with hereditary tyrosinaemia.Biomed. Mass Spectro. 9 (1982) 419–424
Rating, D., Hanefeld, F., Siemes, H., Kneer, J., Jakobs, C., Hermier, M. and Divry, P. 4-Hydroxybutyric aciduria: A new inborn error of metabolism. I. Clinical review.J. Inher. Metab. Dis. 7 Suppl. 1 (1984) 90–92
Rutstein, D. D., Nickerson, R. J., Vernon, A. A., Kishore, P., Veech, R. L., Felver, M. E., Needham, L. L. and Thacker, S. B. 2,3-Butanediol: An unusual metabolite in the serum of severely alcoholic men during acute intoxication.Lancet 2 (1983) 534–537
Thompson, J. A. and Markey, S. P. Quantitative metabolic profiling of urinary organic acids by gas-chromatography mass-spectrometry: Comparison of isolation methods.Anal. Chem. 47 (1975) 1313–1321
Thompson, J. A., Markey, S. P. and Fennessey, P. V. Gas-chromatographic/mass-spectrometric identification and quantitation of tetronic and deoxytetronic acids in urine from normal adults and neonates.Clin. Chem. 21 (1975) 1892–1898
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Brown, G.K., Cromby, C.H., Manning, N.J. et al. Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: Evidence of α-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial β-oxidation. J Inherit Metab Dis 10, 367–375 (1987). https://doi.org/10.1007/BF01799979
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DOI: https://doi.org/10.1007/BF01799979