Succinic semialdehyde dehydrogenase deficiency is an autosomal recessive metabolic disease with nonspecific clinical presentation (mild to severe). This is caused by mutations in the SSADH gene in the chromosome region 6p22, which codes for the NAD (+) - dependent succinic acid semialdehyde dehydrogenase. Reduced levels of activity or complete loss of succinic acid semialdehyde dehydrogenase disrupt degradation of gamma-hydroxybutyric acid (GABA).
First symptoms are usually reported at the age of 11 months, and the median age at diagnosis is 6.6 years. Infants typically present with a slowly progressive or non-progressive encephalopathy associated with hypotension, hyporeflexia, ataxia and an delayed acquisition of motor and linguistic developmental milestones in the first two years of life. Common clinical features continue to be sleep disorders and seizures. The latter occur in more than half of all affected individuals and are usually in the form of generalized tonic-clonic lesions or atypical absences.
Psychologically, the disorder may manifest with attention-deficit hyperactivity disorder, aggressive and self-injurious behavior in early childhood, and obsessive-compulsive disorder in adolescence and adulthood. Ocular symptoms such as nystagmus and motility disorders have also been reported occasionally.
A severe onset form occurs in up to 10% of patients and is characterized by extrapyramidal signs and progressive disease progression. Currently, there is no known established and generally effective therapeutic treatment for SSADH deficiency.