ALDH5A1 Gene: Function, Mutations, and Associated Diseases | SSADH Deficiency

The ALDH5A1 gene encodes succinate semialdehyde dehydrogenase (SSADH), a mitochondrial enzyme that catalyzes the irreversible oxidation of succinate semialdehyde to succinate in the GABA degradation pathway. This enzyme is critical for neurotransmitter metabolism, preventing accumulation of neurotoxic metabolites such as gamma-hydroxybutyrate (GHB). Mutations in ALDH5A1 cause succinate semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria, an autosomal recessive disorder characterized by developmental delay, hypotonia, seizures, and intellectual disability.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa00410: beta-Alanine metabolism

• KEGG hsa00430: Taurine and hypotaurine metabolism

• KEGG hsa00650: Butanoate metabolism

• KEGG hsa04727: GABAergic synapse

• Reactome R-HSA-888593: GABA synthesis

• release

• reuptake and degradation

Succinate semialdehyde dehydrogenase (SSADH) is a homotetrameric mitochondrial enzyme of 535 amino acids (UniProt P51649). It catalyzes the NAD+-dependent oxidation of succinate semialdehyde to succinate, the final step of GABA degradation. The enzyme is expressed predominantly in liver and brain. Deficiency leads to accumulation of GHB and GABA, causing neurological symptoms. The protein contains a mitochondrial targeting sequence and a conserved aldehyde dehydrogenase domain.