Table of Contents - %203740

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%203740
ALPHA-KETOGLUTARATE DEHYDROGENASE DEFICIENCY

Alternative titles; symbols
ALPHA-KGD DEFICIENCY
2-KETOGLUTARATE DEHYDROGENASE DEFICIENCY
OXOGLUTARIC ACIDURIA

Phenotype Gene Relationships
Location Phenotype Phenotype
MIM number		 Gene/Locus Gene/Locus
MIM number
7p13 Alpha-ketoglutarate dehydrogenase deficiency 203740 OGDH 613022

Clinical Synopsis

TEXT
Clinical Features
In 3 males born to first-cousin Algerian parents and presenting with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth, Bonnefont et al. (1992) described a 'new' inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase (see 613022) deficiency. Neurologic deterioration resulted in death at about 30 months of age. Low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis were proposed as an indicator of dysfunction of the tricarboxylic acid cycle. The parents of the 3 sibs were related as first cousins.

Kohlschutter et al. (1982) reported a case of partial alpha-ketoglutarate dehydrogenase deficiency in 2 sibs of a consanguineous Tunisian family. In addition to genetic defects of the tricarboxylic acid cycle, other mechanisms for recessively inherited congenital lactic acidosis include inborn errors of pyruvate metabolism and inborn errors of oxidative phosphorylation.

Guffon et al. (1993) described 2 familial cases of 2-ketoglutarate dehydrogenase deficiency: a sister and brother born of consanguineous Portuguese parents. Axial hypotonia with no head control as late as age 4 years was described in both. Metabolic acidosis with acute episodes of acidotic decompensation and sometimes hypoglycemia occurred during infections. The sister died suddenly after a general anesthesia.

REFERENCES
1. Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A. Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. J. Pediat. 121: 255-258, 1992. [PubMed: 1640293, related citations] [Full Text: Pubget]

2. Guffon, N., Lopez-Mediavilla, C., Dumoulin, R., Mousson, B., Godinot, C., Carrier, H., Collombet, J. M., Divry, P., Mathieu, M., Guibaud, P. 2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case. J. Inherit. Metab. Dis. 16: 821-830, 1993. [PubMed: 8295396, related citations] [Full Text: Pubget]

3. Kohlschutter, A., Behbehani, A., Langenbeck, U., Albani, M., Heidemann, P., Hoffmann, G., Kleineke, J., Lehnert, W., Wendel, U. A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria. Europ. J. Pediat. 138: 32-37, 1982. [PubMed: 7075624, related citations] [Full Text: Pubget]

Creation Date: Victor A. McKusick : 10/2/1992
Edit History: carol : 09/18/2009
alopez : 6/13/2005
terry : 4/18/2005
carol : 3/17/2004
terry : 7/31/1998
mark : 7/9/1997
mark : 10/20/1995
carol : 4/6/1994
mimadm : 3/11/1994
carol : 12/13/1993
carol : 10/13/1992
carol : 10/2/1992