[MIM 271 980]

(SSADH syndrome, 4-hydroxybutyric aciduria)

Prevalence < 1/106. Autosomal recessive inheritance of a mutation in the ALDH5A1 gene (6p22). Disorder of the degradation of GABA, the main inhibitory neurotransmitter of the central nervous system. Succinate-semialdehyde dehydrogenase deficiency leads to an accumulation of GABA and 4-hydroxybutyric acid (or gamma-hydroxybutyrate (GHB)) especially in the central nervous system.

This hyper-GABA-ergic state paradoxically leads to frequent, sometimes lethal seizures. This is probably due to downregulation  of GABAA and probably GABABreceptors. 

• onset around 11-12 months of age
• non- or slightly progressive encephalopathy with hypotonia, hyporeflexia and ataxia
• developmental delay
• severe language disorders
• mental retardation
• epilepsy (> 50 %)
• psychiatric problems
• abnormal movements, ataxia
• obsessive-compulsive disorder
• sleep disorders

In about 10 % of cases: acute presentation in the form of infantile encephalopathy.

Anesthetic implications:

epilepsy, behavioral disorders

References :

-        Pearl PL, DiBacco ML, Papadelis C, Opladen T, Hanson E, Roullet J-B, Gibson KM.
Succinic semialdehyde dehydrogenase deficiency: review oft he natural history study.
J Child Neurol 2021; 36:1153-61

Updated: December 2021