30-70% of patients;unusual, < 30% of patients): Common manifestations include: Delayed gross motor development Delayed mental development Delayed fine motor skill development Delayed speech and language development Hypotonia Frequent manifestations include: Seizures Hyporeflexia Ataxia Behavioral problems Hyperkinesis Unusual manifestations include: Neonatal problems EEG abnormalities Psychoses MRI or X-ray computed tomography abnormalities Oculomotor apraxia Microcephaly Macrocephaly Hyperreflexia Somnolence Choreoathetosis Myopathy Genetics SSADH deficiency is inherited in an autosomal recessive fashion. Such diseases are caused by an error in a single DNA gene. Because the disease is autosomal, the defective gene is found on an autosome (chromosome 6), rather than the sex-linked 23rd chromosome. Being a recessive disorder, the disease can only be inherited from both parents since the disorder can only occur when a person has two copies of the gene. It is believed that the genetic basis for SSADH deficiency resides in the SSADH human ALDH5A1 gene, which maps to chromosome 6p22. More than 47 disease-causing mutations have been identified for the disorder, all of which lead to absence of functional proteins through missense, nonsense, or splicing errors; no hotspots have been identified. Consanguinity is frequent; this suggests the rare occurrence of disease-causing alleles in the general population. Mechanism GABA is a major inhibitory neurotransmitter in the central nervous system. It modulates the activity of several neurotransmitters including dopamine, serotonin, and norepinephrine. GABA is synthesized in a single step from its precursor glutamate by glutamic acid decarboxylase. GABA is metabolized by successive transamination and oxidation to yield succinic semialdehyde and succinic acid respectively via the catalyzing effects of GABA transaminase. The succinic semialdehyde can be converted into either succinic acid by SSADH or to GHB by the enzyme succinic semialdehyde reductase. The absence of SSADH leads to a 30-fold increase of GHB and a 2-4 fold increase of GABA in the brains of patients with SSADH deficiency as compared to normal brain concentrations of the compounds. Elevations of GHB have been shown to induce spike and wave activity similar to that seen in generalized absence epilepsy in animal models as well, which has motivated researchers to increase their knowledge on the relationship between GHB and the neurological manifestations seen in SSADH deficiency. GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple receptors GABAB. The GABAB receptor has been found to be the most important of the three receptors