By: Claire Logan
What is the SLC13A5 Gene?
The SLC13A5 gene provides instructions for making a protein called sodium/citrate cotransporter (NaCT). This protein moves citrate, a key molecule involved in energy production and metabolism, into our cells, especially those in the brain and liver. Inside cells, citrate helps keep chemical signals balanced, supports the building of healthy cell structures, and provides energy the brain needs to function properly. Changes, or variants, in the SLC13A5 gene may reduce or stop the function of the NaCT protein, preventing citrate from entering cells. Without enough citrate in brain cells, the brain’s ability to produce and use energy is disrupted, particularly during early development. This can lead to a rare condition called SLC13A5-related epilepsy, which usually begins in the first days or weeks of life.
SLC13A5–Related Epilepsy
SLC13A5-related epilepsy is typically characterized by seizures that begin in the neonatal period, which is the first four weeks of a baby’s life. These seizures can involve stiffening, jerking, or more subtle movements. In many cases, these seizures do not respond well to standard anti-seizure medications and often recur frequently during early infancy.
As children grow, many continue to experience developmental delays, particularly with motor and speech skills. In addition to developmental delays, other common features include low muscle tone, poor coordination, intellectual disability, and challenges or difficulties with walking and talking. While some individuals may have fewer seizures as they get older, delays in development and movement usually persist. In fact, a 2021 natural history study of 23 individuals with SLC13A5 variants found that all participants had seizures beginning in the neonatal period, and most continued to have significant developmental disabilities as they matured (Klotz et al., 2021). The study also highlighted that the early onset of seizures is a common characteristic in those with SLC13A5 variants, potentially helping clinicians diagnose the condition earlier. Additionally, in most cases, SLC13A5-related epilepsy is not inherited from a parent, but rather, arises randomly during early development.
Research and Treatment
Currently, there is no cure for SLC13A5-related epilepsy, and treatment focuses on managing seizures and supporting the child’s development. Anti-seizure medications, such as phenobarbital, levetiracetam, and topiramate, are commonly used, although their effectiveness varies across individuals. Because variants in the SLC13A5 gene create imbalances in the brain’s chemical messengers, researchers are actively exploring new, more targeted treatments. One promising and upcoming area is gene therapy. Taysha Gene Therapies is developing TSHA-105, a gene replacement therapy designed to restore SLC13A5 function by delivering a healthy copy of the gene. As of 2025, this therapy is still in preclinical development, meaning it is being tested in the lab and has not yet been tried in humans. However, early lab results show promising potential for improving how these affected cells function (Taysha, 2023).
Families navigating SLC13A5-related epilepsy often need support from a multidisciplinary care team, including neurologists, genetic counselors, developmental pediatricians, physical therapists, and speech-language pathologists. Because this condition can be challenging to diagnose, raising and spreading awareness among healthcare providers is crucial for early intervention and better outcomes.
Resources:
“What Is SLC13A5 Citrate Transporter Disorder?” TESS Research Foundation, www.tessfoundation.org/slc13a5. Accessed 25 June 2025.
Klotz, Katja A., et al. “SLC13A5 Deficiency Disorder: A Natural History Study.” Epilepsia Open, vol. 6, no. 2, 2021, pp. 366–374. https://doi.org/10.1002/epi4.12472.
“Taysha Gene Therapies Announces New Data on TSHA-105.” Taysha Gene Therapies, 2023. https://www.tayshagtx.com/news-media (Accessed 25 June 2025).
