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Characterized by hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. The life expectancy is limited to about 30 months of age. Death is caused by neurologic deterioration. Other clinical features include axial hypotonia with no head control until late in childhood. Metabolic acidosis with acute episodes of acidotic decompensation and sometimes hypoglycemia may occur during infections. Low plasmatic molar ratios of ketone bodies in neonate with congenital lactic acidosis have been suggested as an indicator of dysfunction of the tricarboxylic acid cycle.

Alpha-KGD deficiency; 2-Alpha-ketoglutarate dehydrogenase deficiency; Oxoglutaric aciduria; Oxoglutarate dehydrogenase.

There are no epidemiological studies to establish the incidence. A total of 9 infants with isolated alpha-ketoglutarate dehydrogenase deficiency have been reported in the literature. All reported cases are from Northern Africa, mostly Algeria and Tunisia. It is believe that this medical condition is inherited as an autosomal recessive trait.

Alpha-ketoglutarate dehydrogenase is an enzyme of the Krebs cycle that catalyzes the oxidation of alpha-ketoglutarate to succinyl CoA. It is one of 3 alpha-ketoacid dehydrogenase enzymes, the others being pyruvate dehydrogenase and branched-chain ketoacid dehydrogenase. Each of these enzymes is a complex of multiple units. Each unit has 3 distinct subunits. The E1 (alpha-ketoacid decarboxylase), E2 (dihydrolipoyl transacetylase) and E3 (dihydrolipoyl dehydrogenase or lipoamide dehydrogenase) are identical in all 3 alpha-ketoacid dehydrogenases. Alpha-ketoglutarate dehydrogenase, fumarase, and succinate dehydrogenase are the only enzymes of the human Krebs cycle in which a single enzyme deficiency state has been defined.

The clinical presentation includes severe hypotonia, metabolic acidosis, congenital lactic acidosis, early childhood death. Laboratory investigations reveal hyperlactatemia and alpha-ketoglutarate dehydrogenase deficiency.

An arterial blood gas analysis, serum electrolytes, cell blood count and differential must be obtained preoperatively. Patients presenting severe neurological dysfunction may present with seizure activities, airway problems and postoperative complications. Intraoperative cardiovascular instability is possible as a result of electrolyte disturbances. It is essential to correct any intravascular volume deficit and electrolyte imbalances before all elective surgical procedures. Intravenous fluid solutions that contain lactate must be avoided. Postoperative admission to an ICU or a constant care facility may be indicated depending on the severity of the case and the type of surgical procedure performed.

Variable and prolonged response to neuromuscular relaxants should be expected and the use of a peripheral nerve stimulator is recommended to assess degree of neuromuscular blockade during general anesthesia. In the presence of severe hypotonia, it is recommended to avoid the use of succinylcholine.

Guffon N, Lopez-Mediavilla C, Dumoulin R, et al: 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]
Kohlschutter A, Behbehani A, Langenbeck Uet, al: A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria. Europ J Pediat 138:32-37, 1982.  [PubMed: 7075624]

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