Author: Jacob Tiller
The SLC6A1 Gene is responsible for the encoding of a transporter that removes the GABA from a place called the synaptic cleft, the gap between brain cells. GABA is an important inhibitory neurotransmitter, meaning it helps regulate overactivity in brain cells. When a mutation occurs, and the SLC6A1 gene is no longer able to encode a protein responsible for keeping the correct level of GABA in the brain, over-regulation can occur where due to the high level of GABA in the synaptic cleft, neurons cannot communicate properly.
The first indicators of such a disorder can be seen in children who do not meet developmental milestones at expected times. Unfortunately, seizures can also be the first symptom for those suffering from a SLC6A1 genetic mutation and usually arise around the age of two. These seizures will manifest themselves in one of three categories- absence seizures, atonic seizures, and myoclonic seizures. Absence seizures are characterized by overactivity in both hemispheres of the brain, atonic seizures are marked by a sudden loss of muscle strength, and myoclonic seizures are those characterized by brief muscle spasms. Symptoms can range from mild to severe with some children not experiencing seizures at all. Despite this, there are common, less physically traumatic symptom sets including decreased muscle tone, ataxia (lack of muscle control), and tremors. In addition to a lack of physical control, children with SLC6A1 may also experience intellectual deficits such as behavioral disorders in the form of aggression or learning disabilities which often result in an autism diagnosis.
Specific testing is required to officially diagnose a child with a SLC6A1 related disorder and can include EEGs to find irregular brain activity along with MRIs to identify changes in the very structure of the brain. Regarding treatment, although there is not yet a definite cure for SLC6A1 related disorders, methods of phenotypic symptom regulation are available. According to the Children’s Hospital of Philadelphia, seizure medications are often administered to control seizures depending on the type being experienced by each patient. In extreme cases, devices can even be implanted to monitor and regulate brain activity in the form of responsive neurostimulation. Additionally, genetic therapies are being developed to offer a more long-lasting solution to the mutation while both glycerol phenylbutyrate and sodium phenylbutyrate have been shown to improve conditions in clinical trials.
At SLC6A1, our team of researchers is working hard to make strides towards a cure, as unfortunately, one does not currently exist. Advances in gene therapy are currently being made using mice given the SLC6A1 condition to study as models for humans. For any more questions regarding specific research or personnel, please refer to the “Current Research” or the “Board of Medical” advisors tab on the website! Currently, SLC6A1 Connect offers several patient resources to aid you and your loved ones in the aftermath of a diagnosis. Among these resources are recommended medical professionals, further informational sites, diagnoses registrations, and donation links. Here at SLC6A1 Connect we are always working to find a cure and will provide regular updates on scientific findings. For any further questions feel free to contact Mrs. Freed or any of our scientific officers!