Journal of Inherited Metabolic Disease

, Volume 16, Issue 5, pp 821–830

2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: Report of a new case

Authors

  • N. Guffon
    • Service de Pédiatrie et GénétiqueHôpital Debrousse
  • C. Lopez-Mediavilla
    • Laboratoire de Biologie et Technologie des Membranes du CNRSUniversité Claude Bernard, Lyon 1
  • R. Dumoulin
    • Centre d'Etude des Maladies MétaboliquesHôpital Debrousse
  • B. Mousson
    • Centre d'Etude des Maladies MétaboliquesHôpital Debrousse
  • C. Godinot
    • Laboratoire de Biologie et Technologie des Membranes du CNRSUniversité Claude Bernard, Lyon 1
  • H. Carrier
    • Département de Recherches Neuromusculaires, CNRS EP18Faculté de Médecine A. Carrel
  • J. M. Collombet
    • Centre d'Etude des Maladies MétaboliquesHôpital Debrousse
  • P. Divry
    • Centre d'Etude des Maladies MétaboliquesHôpital Debrousse
  • M. Mathieu
    • Centre d'Etude des Maladies MétaboliquesHôpital Debrousse
  • P. Guibaud
    • Service de Pédiatrie et GénétiqueHôpital Debrousse
Article

DOI: 10.1007/BF00714273

Cite this article as:
Guffon, N., Lopez-Mediavilla, C., Dumoulin, R. et al. J Inherit Metab Dis (1993) 16: 821. doi:10.1007/BF00714273

Summary

Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.

Copyright information

© SSIEM and Kluwer Academic Publishers 1993