Succinic semialdehyde dehydrogenase deficiency is one of the disorders of
GABA metabolism, so it is not surprising that
seizures occur as one of the symptoms in affected patients. Other features that are described include delayed development,
hypotonia,
myopathy with ragged red fibres, abnormal behaviour, and ocular abnormalities. Neonatal problems include prematurity, respiratory difficulties, and hypoglycaemia. The responsible gene has been identified on the short arm of chromosome 6. There are many mutations, and there is poor genotype-phenotype correlation resulting in difficulties in diagnosis. The pathogenesis of the condition is discussed, especially the results of the disturbed
GABA catabolism, and the production of the
gamma-hydroxybutyric acid. The many properties of this substance suggest it may act as a
neurotransmitter or
neuromodulator in the brain. The diagnosis may be difficult as the clinical picture is not really suggestive, but the MRI examination can help if it shows abnormalities in the globus pallidus. It will be confirmed by finding an excess of
4-hydroxybutyric acid in the body fluids; and the methods of estimation are discussed. Prenatal diagnosis is possible using a combination of methods. Treatment possibilities are limited.
Vigabatrin should be of value as it is an inhibitor of
GABA transaminase, but results have been disappointing. Symptomatic treatment may well be needed for control of
seizures, abnormal behaviour and other disorders; and special educational needs must be served.