Introduction
Alpha-Ketoglutarate dehydrogenase (2-KGD) deficiency, a rare disorder of
the Krebs cycle, was described for the first time as a progressive
neurodegenerative disease with 2-ketoglutaric aciduria in two siblings
of a Tunisian consanguineous family by Kohlschutter and colleagues
(1982) [1]. Alpha-Ketoglutarate dehydrogenase is a multienzyme
complex that catalyzes the oxidative decarboxylation of a-ketoglutarate
to succinyl-coenzyme A in the tricarboxylic acid cycle. It is made up of
three components:
- E1 a-ketoglutarate lipoamide oxidoreductase.
- E2 dihydrolipoamide succinyltransferase transfers the carboxyl group
to the coenzyme A moiety.
- E3 dihydrolipoamide dehydrogenase transfers reducing oxygen from E2 to
a flavoprotein and finally to nicotinamide-adenine dinucleotide.
Onset and clinical presentation of the reported cases of the (2-KGD)
deficiency are heterogeneous, with mostly severe neurological
impairment, including muscular hypotonia, developmental delay,
extrapyramidal symptoms, ataxia, increased extensor tonus, and seizures.
The age of onset varied between the neonatal period and 16 months. The
oldest child reported died at the age of 10 years [1, 2, and 3].