Absence of hepatic molybdenum cofactor: An inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase
Five patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, probably, also of aldehyde oxidase are described. This remarkable coincidence of three inborn errors of metabolism in a single individual was demonstrated to result from a deficiency of the ‘molybdenum cofactor’, an essential constituent of all three enzymes. The main biochemical findings in these patients included: hypouricaemia, xanthinuria, an increased excretion of sulphite, thiosulphate andS-sulphocysteine and a decreased excretion of inorganic sulphate. Plasma molybdenum was normal. The ultimate diagnosis was made by the measurement of ‘molybdenum cofactor’ in a liver biopsy specimen in three out of five patients.
The clinical hallmarks in these patients were: feeding difficulties, mental retardation, neurological symptoms, lens dislocation, an abnormal muscle tone, myoclonia and an abnormal physiognomy. The majority of these were already present in the neonatal period. So far, attempts at treatment have been unsuccessful.
KeywordsMolybdenum Inborn Error Sulphite Thiosulphate Biochemical Finding
Unable to display preview. Download preview PDF.
- Irreverre, F., Mudd, S. H., Heizer, W. D. and Laster, L. Sulfite oxidase deficiency: Study of a patient with mental retardation, dislocated ocular lenses, and abnormal urinary excretion of S-sulfo-L-cysteine, sulfite and thiosulfate.Biochem. Med. 1 (1967) 187–217Google Scholar
- Johnson, J. L. The molybdenum cofactor common to nitrate reductase, xanthine dehydrogenase and sulphite oxidase. In Coughlan, M. P. (ed.)Molybdenum and Molybdenum-containing Enzymes, Pergamon, Oxford, 1980, pp. 345–383Google Scholar
- Johnson, J. L., Waud, W. R., Rajagopalan, K. V., Duran, M., Beemer, F. A. and Wadman, S. K. Inborn error of molybdenum metabolism. Combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor.Proc. Natl. Acad. Sci. USA 77 (1980a) 3715–3719PubMedGoogle Scholar
- Shih, V. E., Abroms, I. F., Johnson, J. L., Carney, M., Mandell, R., Robb, R. M., Clotherty, J. P. and Rajagopalan, K. V. Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfurmetabolism.N. Engl. J. Med. 297 (1977) 1022–1028PubMedGoogle Scholar
- Wadman, S. K., de Bree, P. K., van Gennip, A. H., Stoop, J. W., Zegers, B. J., Staal, G. E. J. and Siegenbeek van Heukelom, L. H. Urinary purines in a patient with a severely defective T cell immunity and a purine nucleoside phosphorylase deficiency. In Müller, M. M., Kaiser E. and Seegmiller, J. E. (eds.)Purine Metabolism in Man II, Plenum, New York, (1977) pp. 471–476Google Scholar