Abstract
A severely mentally retarded infant with congenital lactic acidosis due to pyruvate carboxylase deficiency is reported. The patient suffered from vomiting and convulsions soon after birth and developed severe mental and motor retardation at 3 months of age.
The persistent elevation of pyruvate and lactate in both blood and cerebrospinal fluid and hyperalanaemia suggested an impairment of pyruvate oxidation. The enzyme activities of pyruvate carboxylase in both liver tissues and cultured skin fibroblasts of the patient revealed values of about 5% of controls. However, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase activities in liver tissues were within normal limits.
The patient had no response to administration of large doses of thiamine, lipoic acid and biotin, clinically and biochemically.
A prenatal diagnosis was performed in the second pregnancy and the pyruvate carboxylase activities of the cultured amniotic fluid cells obtained by amniocentesis were within normal limits.
Similar content being viewed by others
References
Atkin, B. M. Carrier detection of pyruvate carboxylase deficiency in fibroblasts and lymphocytes.Pediatr. Res. 13 (1979) 1101–1104
Atkin, B. M., Buist, N. R. M., Utter, M. F., Leiter, A. B. and Banker, B. Q. Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease.Pediatr. Res. 13 (1979a) 109–116
Atkin, B. M., Utter, M. F. and Weinberg, M. B. Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in leucocytes and fibroblasts from a patient with pyruvate carboxylase deficiency.Pediatr. Res. 13 (1979b) 38–43
Blass, J. P., Avigan, J. and Uhlendorf, B. W. A defect in pyruvate decarboxylase in a child with an intermittent movement disorder.J. Clin. Invest. 49 (1970) 423–432
Cooper, J. R., Itokawa, Y. and Pincus, J. H. Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy.Science 164 (1969) 72–75
Evance, O. B. Pyruvate carboxylase deficiency in subacute necrotizing encephalomyelopathy.Arch. Neurol. 38 (1981) 515–519
Farrell, D. F., Clark, A. F., Scott, C. R. and Wennberg, R. P. Absence of pyruvate decarboxylase activity in man: A cause of congenital lactic acidosis.Science 187 (1975) 1082–1084
Feldman, G. L. and Wolf, B. Measurement of pyruvate carboxylase activity in amniotic fluid cells.Pediatr. Res. 14 (1979) 153
Hansen, T. L. and Christensen, E. Studies on pyruvate carboxylase from cultured human fibroblasts and amniotic fluid cells.J. Inher. Metab. Dis. 2 (1979) 23–28
Hayakawa, T., Hirashima, N., Ibe, S., Hamada, M., Okabe, K. and Koike, M. Mammalian α-keto acid dehydrogenase complexes.J. Biol. Chem. 241 (1966) 4694–4699
Hommes, F. A., Polman, H. A. and Reerink, J. D. Leigh's encephalomyelopathy: an inborn error of gluconeogenesis.Arch. Dis. Child. 43 (1968) 423–426
Hommes, F. A., Schrijver, J. S. and Dias, Th. Pyruvate carboxylase deficiency, studies on patients and on an animal model system. In Burman, D., Holton, J. B. and Penndock, C. A. (eds.)Inherited Disorders of Carbohydrate Metabolism, MTP Press, Lancaster, 1980, pp. 269–288
Israels, S., Haworth, H. C., Dunn, H. G. and Applegarth, D. A. Lactic acidosis in childhood.Adv. Pediatr. 22 (1976) 267–303
Lowry, O. H., Rosebrough, N. J., Farr, A. and Randall, R. J. Protein measurements with the folin phenol reagent.J. Biol. Chem. 193 (1951) 265–275
Marsac, C., Augereau, Ch., Feldman, G., Wolf, B., Hansen, T. L. and Berger, R. Prenatal diagnosis of pyruvate carboxylase deficiency.Clin. Chim. Acta. 119 (1982) 121–127
Murphy, J. V., Isohashi, F., Weinberg, M. B. and Utter, M. F. Pyruvate carboxylase deficiency. An alleged biochemical cause of Leigh's disease.Pediatrics 68 (1981) 401–404
Tsuchiyama, A., Sogawa, H., Oyanagi, K., Nakao, T., Ogawa, K. and Fujita, S. Normal activities of hepatic pyruvate dehydrogenase and pyruvate carboxylase in Leigh's syndrome.Tohoku. J. Exp. Med. 139 (1983) 67–72
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsuchiyama, A., Oyanagi, K., Hirano, S. et al. A case of pyruvate carboxylase deficiency with later prenatal diagnosis of an unaffected sibling. J Inherit Metab Dis 6, 85–88 (1983). https://doi.org/10.1007/BF01800730
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01800730