Disorders of gamma aminobutyric acid metabolism Save

Disorders of gamma aminobutyric acid (GABA) metabolism are a group of rare genetic disorders that affect the body's ability to produce or utilize GABA, a neurotransmitter that plays a crucial role in regulating brain activity. These disorders can lead to a range of neurological symptoms, including seizures, developmental delays, and intellectual disabilities.

One of the most well-known disorders of GABA metabolism is GABA transaminase deficiency (GABAT), which is caused by mutations in the ABAT gene. This gene provides instructions for making an enzyme called GABA transaminase, which helps break down GABA in the brain. In people with GABAT deficiency, GABA levels in the brain become elevated, leading to seizures, developmental delays, and other neurological problems. Treatment typically involves medications to help control seizures and other symptoms.

Another disorder of GABA metabolism is succinic semialdehyde dehydrogenase deficiency (SSADH), which is caused by mutations in the ALDH5A1 gene. This gene provides instructions for making an enzyme called SSADH, which is involved in breaking down GABA in the brain. In people with SSADH deficiency, GABA accumulates in the brain, leading to a range of neurological symptoms, including seizures, ataxia (difficulty coordinating movements), and intellectual disabilities. Treatment typically involves medications to control seizures and other symptoms.

A third disorder of GABA metabolism is pyridoxine-dependent epilepsy (PDE), which is caused by mutations in the ALDH7A1 gene. This gene provides instructions for making an enzyme called antiquitin, which is involved in the breakdown of lysine, an amino acid found in many foods. In people with PDE, the breakdown of lysine is impaired, leading to the accumulation of toxic byproducts that interfere with the production of GABA in the brain. Treatment involves large doses of vitamin B6 (pyridoxine), which can help restore GABA production and control seizures.

Other disorders of GABA metabolism include GABA receptor mutations, which affect the body's ability to respond to GABA, and GABA transporter defects, which impair the transport of GABA across cell membranes. These disorders are also associated with a range of neurological symptoms and are typically treated with medications to control seizures and other symptoms.

Overall, while disorders of GABA metabolism are rare, they can have serious neurological consequences. However, with proper diagnosis and treatment, many people with these disorders can lead fulfilling lives. Ongoing research into the underlying causes of these disorders may lead to new treatments and improved outcomes for affected individuals.