| Succinic semialdehyde dehydrogenase deficiency | |
|---|---|
| Other names | 4-hydroxybutyric aciduria or Gamma-hydroxybutyric aciduria, |
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| Gamma-Hydroxybutyric acid | |
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder[1] of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families.[2] The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.[3]
SSADH deficiency is caused by an enzyme deficiency in GABA degradation. Under normal conditions, SSADH works with the enzyme GABA transaminase to convert GABA to succinic acid. Succinic acid can then be utilized for energy production via the Krebs cycle. However, because of the deficiency, the final intermediate of the GABA degradation pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric dehydrogenase. This causes elevations in GHB and is believed to be the trademark of this disorder and cause for the neurological manifestations seen.[2]
- ^ Chambliss, K. L.; Hinson, D. D.; Trettel, F.; Malaspina, P.; Novelletto, A.; Jakobs, C.; Gibson, K. M. (1998). "Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria)". American Journal of Human Genetics. 63 (2): 399–408. doi:10.1086/301964. PMC 1377305. PMID 9683595.
- ^ a b Pearl, P. L.; Novotny, E. J.; Acosta, M. T.; Jakobs, C.; Gibson, K. M. (2003). "Succinic semialdehyde dehydrogenase deficiency in children and adults". Annals of Neurology. 54 (Suppl 6): S73–80. doi:10.1002/ana.10629. PMID 12891657. S2CID 34085564.
- ^ Jakobs, C.; Jaeken, J.; Gibson, K. M. (1993). "Inherited disorders of GABA metabolism". Journal of Inherited Metabolic Disease. 16 (4): 704–715. doi:10.1007/BF00711902. PMC 3675887. PMID 8412016.