Pyruvate Carboxylase Deficiency

  • Marjo S. van der Knaap
  • Jacob Valk

Abstract

Pyruvate carboxylase (PC) deficiency is a rare disorder with autosomal recessive inheritance. Generally, two clinical and biochemical phenotypes of isolated PC deficiency can be distinguished. The so-called French phenotype presents in the neonatal period with severe lactic acidemia and is clinically characterized by failure to thrive, anorexia, vomiting, weak cry, convulsions, stupor, hyporeactivity, hypotonia, tachypnea, dyspnea, respiratory failure, and subsequently hypertonia, extrapyramidal tract signs and severely retarded development. Most children die within the first few months of life. The North American phenotype is less severe. Patients become symptomatic between 2 and 5 months of age with developmental delay, failure to thrive, apathy, hypotonia, spasticity, ataxia, nystagmus and convulsions. Episodes of vomiting, tachypnea, tachycardia, ataxia and lactic acidosis occur, precipitated by metabolic or infectious stress. Some patients die in the infantile period, while most of the survivors are grossly retarded. A few exceptional patients have been reported who despite the episodic metabolic derangement have a normal or near normal motor and mental development. Formerly, Leigh syndrome was thought to represent another clinical phenotype of PC deficiency, but this could not be confirmed.

Keywords

Lactate Proline Lysine Ketone Pyruvate 

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References

  1. Atkin BM, Buist NRM, Utter MF, Leiter AB, Banker BQ (1979) Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leighs disease. Pediatr Res 13: 109116Google Scholar
  2. Augereau C, Dinh DP, Moncion A, Marsac C, Saudubray JM, Robinson BH (1985) Pyruvate carboxylase deficiencies: complementation studies between „French“ and „American” phenotypes in cultured fibroblasts. J Inherited Metab Dis 8: 59–62PubMedCrossRefGoogle Scholar
  3. Baal MG, Gabreëls FJM, Renier WO, Hommes FA, Gijsbers THJ, Lamers KJB, Kok JCN (1981) A patient with pyruvate carboxylase deficiency in the liver: treatment with aspartic acid and thiamine. Dev Med Child Neurol 23: 521–530PubMedCrossRefGoogle Scholar
  4. Bartlett K, Ghneim HK, Stirk JH, Dale G, Alberti GMM (1984) Pyruvate carboxylase deficiency. J Inherited Metab Dis 7 Suppl 11: 74–78CrossRefGoogle Scholar
  5. Farkas-Bargeton E, Goutières F, Richardet JM, Thieffry S, Brissaud HE (1971) Leucoencéphalopathie familiale associée à une acidose lactique congénitale. Acta Neuropathol (Berl) 17: 156–168CrossRefGoogle Scholar
  6. Feldman GL, Wolf B (1980) Evidence for two genetic complementation groups in pyruvate carboxylase-deficient human fibroblast cell lines. Biochem Genet 18: 617–624PubMedCrossRefGoogle Scholar
  7. Greter J, Gustafsson J, Holme E (1985) Pyruvate-carboxylase deficiency with urea cycle impairment. Acta Paediatr Scand 74: 982–986PubMedCrossRefGoogle Scholar
  8. Hansen TL, Christensen E, Willems JL, Trijbels JMF (1983) A mutation of pyruvate carboxylase in fibroblasts from a patient with severe, chronic lactic acidaemia. Clin Chim Acta 131: 39–44PubMedCrossRefGoogle Scholar
  9. Hansen TL, Christensen E, Brandt NJ (1982) Studies on pyruvate carboxylase, pyruvate decarboxylase and lipoamide dehydrogenase in subacute necrotizing encephalomyelopathy. Acta Paediatr Scand 71: 263–267PubMedCrossRefGoogle Scholar
  10. Higgins JJ, Glasgow AM, Lusk M, Kerr DS (1994) MRI, clinical, and biochemical features of partial pyruvate carboxylase deficiency. J Child Neurol 9: 436–439PubMedCrossRefGoogle Scholar
  11. Maesaka H, Komiya K, Misugi K, Tada K (1976) Hyperalaninemia, hyperpyruvicemia and lactic acidosis due to pyruvate carboxylase deficiency of the liver; treatment with thiamine and lipoic acid. Eur J Pediatr 122: 159–168PubMedCrossRefGoogle Scholar
  12. Murphy JV, Isohashi F, Weinberg MB, Utter MF (1981) Pyruvate carboxylase deficiency: an alleged biochemical cause of Leighs disease. Pediatrics 68: 401–404PubMedGoogle Scholar
  13. Oizumi J, Donnell GN, Ng WG, Mulivor RA, Greene AE, Coriell LL (1984) Congenital lactic acidosis associated with pyruvate carboxylase deficiency. Cytogenet Cell Genet 38: 81CrossRefGoogle Scholar
  14. Oizumi J, Ng WG, Donnell GN (1986) Pyruvate carboxylase defect: metabolic studies on cultured skin fibroblasts. J Inherited Metab Dis 9: 120–128PubMedCrossRefGoogle Scholar
  15. Perry TL, Haworth JC, Robinson BH (1985) Brain amino acid abnormalities in pyruvate carboxylase deficiency. J Inherited Metab Dis 8: 63–66PubMedCrossRefGoogle Scholar
  16. Pollock MA, Cumberbatch M, Bennett MJ, Gray RGF, Brand M, Hyland K, Congdon PJ, Pitts-Tucker T, Gray S (1986) Pyruvate carboxylase deficiency in twins. J Inherited Metab Dis 9: 29–30PubMedCrossRefGoogle Scholar
  17. Robinson BH (1989) Lactic acidemia: biochemical, clinical, and genetic considerations. Adv Hum Genet 18:151–179, 371–372Google Scholar
  18. Robinson BH, Oei J, Sherwood WG, Applegarth D, Wong L, Haworth J, Goodyer P, Casey R, Zaleski LA (1984) The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency. Am J Hum Genet 36: 283–294PubMedGoogle Scholar
  19. Robinson BH, Toone JR, Benedict P, Dimmick JE, Oei J, Applegarth DA (1985) Prenatal diagnosis of pyruvate carboxylase deficiency. Prenat Diagn 5: 67–71PubMedCrossRefGoogle Scholar
  20. Robinson BH, Oei J, Saudubray JM, Marsac C, Bartlett K, Quan F, Gravel R (1987) The French and North American phenotypes of pyruvate carboxylase deficiency, correlation with biotin containing protein by 3H-biotin incorporation, 35S-streptavidin labeling, and northern blotting with a cloned cDNA probe. Am J Hum Genet 40: 50–59PubMedGoogle Scholar
  21. Rutledge SL, Snead OC, Kelly DR, Kerr DS, Swann JW, Spink DL, Martin DL (1989) Pyruvate carboxylase deficiency: acute exacerbation after ACTH treatment of infantile spasms. Pediatr Neurol 5: 249–252PubMedCrossRefGoogle Scholar
  22. Sander J, Packman S, Berg BO, Hutchison HT, Caswell N (1984) Pyruvate carboxylase activity in subacute necrotizing encephalopathy ( Leighs disease ). Neurology 34: 515–516Google Scholar
  23. Saudubray JM, Marsac C, Charpentier C, Cathelineau L, Leaud MB, Leroux JP (1976) Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings. Acta Paediatr Scand 65: 717–724PubMedGoogle Scholar
  24. Tsuchiyama A, Oyanagi K, Hirano S, Tachi N, Sogawa H, Wagatsuma K, Nakao T, Tsugawa S, Kawamura Y (1983) A case of pyruvate carboxylase deficiency with later prenatal diagnosis of an unaffected sibling. J Inherited Metab Dis 6: 85–88PubMedCrossRefGoogle Scholar
  25. Van Coster RN, Fernhoff PM, De Vivo DC (1991) Pyruvate carboxylase deficiency: a benign variant with normal development. Pediatr Res 30: 1–4PubMedCrossRefGoogle Scholar
  26. Wong LTK, Davidson GF, Applegarth DE, Dimmick JE, Norman MG, Toone JR, Pirie G, Wong J (1986) Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. Pediatr Res 20: 274–279PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Marjo S. van der Knaap
    • 1
  • Jacob Valk
    • 2
  1. 1.Department of Child NeurologyFree University HospitalAmsterdamThe Netherlands
  2. 2.Department of Diagnostic RadiologyFree University HospitalAmsterdamThe Netherlands

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