Succinate-semialdehyde dehydrogenase, mitochondrial (ALDH5A1) (ALDH5A1)

Succinate-semialdehyde dehydrogenase (ALDH5A1) is a mitochondrial enzyme responsible for the final step of the GABA degradation pathway, converting succinic semialdehyde into succinate for use in the TCA cycle. A deficiency in this enzyme leads to the rare genetic disorder SSADHD, which causes a toxic buildup of GABA and gamma-hydroxybutyrate (GHB) in the central nervous system, resulting in severe neurological and psychiatric symptoms. Therapeutic strategies like GAL301-mediated gene expression aim to upregulate the production of functional ALDH5A1 to restore metabolic balance. By increasing the expression of the ALDH5A1 gene, these treatments seek to alleviate the developmental delays, seizures, and cognitive impairments associated with the deficiency. This approach represents a shift from symptomatic management toward addressing the underlying genetic and enzymatic cause of the disease.

Other names

Aldehyde dehydrogenase 5 family member A1Succinate-semialdehyde dehydrogenaseSSADHSSDH4-hydroxybutyrate dehydrogenaseNAD(+)-dependent succinic semialdehyde dehydrogenase

Induction of ALDH5A1 gene expression to restore enzymatic activity and reduce toxic accumulation of GABA and GHB.