A number of pharmacological treatments have been suggested or tested for efficacy on Aldh5a1-/- mice and/or humans. Below is a small sampling of the most common treatments though to be therapeutic to patients with<unk> . Unfortunately, there is very little data to support the benefit of the following treatments since few controlled studies have been conducted in patients. Two hallmarks of SSADH disorder are the increased levels of both GHB and GABA. Potential treatment modalities into biochemical and neurological correction should aim to reduce one or both while not exacerbating the other. Vigabatrin The most common therapeutic agent available for<unk>  is one that reduces the levels of GHB via inhibition of GABA transaminase. Vigabatrin is an irreversible inhibitor of GABA transaminases which leads to decreased levels of GHB and elevation of GABA. Clinical results after use are diverse, ranging from improved ataxia and speech in some patients to worsening of symptoms in others. Lower doses (30–50 mg/kg per day) is associated with fewer side effects and greater improvement of clinical features at high doses of the therapeutic. Although vigabatrin has not been consistently successful in patients with<unk> , it has shown enhanced survival of Aldh5a1-/- mice at very high doses. Sodium valproate Sodium valproate has been used for the treatment of generalized and partial seizures in humans for both epilepsy and bipolar disorder. Valproate enhances GABA synthesis and release leading to augmented GABAergic functions in some areas of the brain. Successful interventions with valproate have been noted, but no clinical trials have been conducted thus far. However, Valproate is usually contraindicated as it may inhibit residual SSADH enzyme activity. GABAB receptor antagonist: CGP-35348 The GABAB antagonist CGP-35348 (3-amino-propyl-(diethoxymethyl) phosphinic acid) has been used in Aldh5a1-/- mice with strong results. It has shown to reduce the frequency of absence seizures, though there have been some cases in which it worsened convulsive seizures. GABAB agonist: baclofen Baclofen (β-p-chlorophenyl-GABA) has some analgesic properties and has been traditionally used for spasticity. Its pharmacological effects primarily take place via presynaptic GABAB receptors in the spinal cord, simultaneously releasing excitatory neurotransmitters onto motor neurons. Because the number and function of GABAB receptors has been shown to progressively diminish in Aldh5a1-/- mice, such a therapy may prove to be useful. However, no data on the efficacy of baclofen on Aldh5a1-/- mice or human patients has been reported. Taurine Taurine is a non-protein sulfur amino acid that is found in high concentrations in human milk. It has been shown to have neuroprotective and neuromodulating properties. While it is an inhibitory neurotransmitter, its ability to cross the blood brain barrier is limited. There is a lot of literature that indicates that taurine acts as antagonist at GABAA and GABAB receptors which may further enhance its ability to treat patients with<unk> , but further pharmacological studies are yet to be conducted to see if taurine could serve a therapeutic purpose. Taurine has been successfully used in a single case open study in a child with<unk> ; with resolving of brain lesions, and improvement in coordination and gait. Ketogenic diet During prolonged periods of fasting, ketone bodies serve as the primary energy source for the brain. In 2006, Henderson et al. showed that there is a therapeutic effect of maintaining a ketogenic diet – a diet consisting of high fat/low carbohydrate meals – in children with epilepsy. Ketogenic diets have also been shown to have some neuroprotective effects in models of Parkinson's disease and hypoxia as well. In a recent study conducted at the Hospital for Sick Children in Canada in 2007, researchers found that a ketogenic diet prolonged the lifespan of Aldh5a1-/- mice by greater than 300%, along with the normalization of ataxia and some improvement in various seizure types seen in SSADH deficient murine models. These effects were in conjunction with "...a significant restoration of GABAergic synaptic activity and region-specific restoration of GABAA receptor associated chloride channel binding." Ultimately, the data seen in the study indicated that a ketogenic diet may work in its ability to restore GABAergic inhibition. But further studies on murine models need to be conducted, ultimately leading to the possibility of conducting a controlled study on humans afflicted with the disorder. There is speculation that a ketogenic diet may be harmful for humans with<unk>  as it may cause elevated levels of GHB in the bloodstream. Other interventions Other therapeutic interventions include: * ethosuximide and other anticonvulsant drugs * GHB receptor antagonist NCS-382 * GABAA receptor modulators * uridine * acamprosate * dopaminergic agents * dextromethorphan * glutamine * antioxidants * Lamotrigine The GABA(B) receptor antagonist, SGS-742, is currently being tested as a potential therapeutic in an NIH phase II clinical trial (NCT02019667).
Succinic semialdehyde dehydrogenase deficiency
Pyruvate dehydrogenase deficiency
2-Methylbutyryl-CoA dehydrogenase deficiency
3-Methylcrotonyl-CoA carboxylase deficiency
Malonyl-CoA decarboxylase deficiency
Glutaminase deficiency
Pyruvate kinase deficiency
Succinyl-CoA:3-oxoacid CoA transferase deficiency