Understanding SLC13A5

What’s in a Name?

The Basics…
SLC13A5 Epilepsy is a newly discovered disorder with many names. First described in July of 2014, SLC13A5 Epilepsy is a neurological disorder associated with the gene SLC13A5. This gene codes for a protein that is responsible for transporting citrate. Mutations in this gene cause epilepsy starting in the first few days of life and developmental problems.

A Trick to Remember…
We know that SLC13A5 is hard to say and difficult to remember. Here are some mnemonic tricks that help us remember the gene name:

SLC: think of Salt Lake City. This will help you remember the order of the first 3 letters
13: unlucky 13 is memorable for those of us who are superstitious!
A5: a standard size of paper in Europe

Do you have any good tricks to remember SLC13A5? If so, share them with us at info@tessfoundation.org!

In More Technical Terms…
Here is a chart to help you unravel the many names of SLC13A5 Epilepsy:

The NameWhat does this name mean?Who uses this name?
SLC13A5 EpilepsyThis name combines the name of the gene (SLC13A5) plus the most well known symptom of the disease (Epilepsy). TESS Research Foundation, donors, clinicians, and affected families.
SLC13A5 Citrate Transporter DisorderThis name combines the gene name (SLC13A5) and the function of the gene (Citrate Transport).TESS Research Foundation encourages the use of this gene/protein name in all scientific publications. Due to its length (it’s a mouthful!), this name is not as popular among affected families.
Citrate Transporter DisorderThis name highlights that the SLC13A5 gene is responsible for transporting citrate.Some doctors and scientists.
SLC13A5 DeficiencyThis name combines the name of the gene (SLC13A5) and indicates that changes to this gene result in a loss of function or a deficiency of the transporter.TESS Research Foundation used to use this name, however some families do not like the term ‘deficiency’ because it sounds negative. TESS now uses SLC13A5 Epilepsy as the default term on our website and in educational materials.
Early Infantile Epileptic Encephalopathy 25 (EIEE25)This is the name formerly used by OMIM. It combines when symptoms start (early infancy) plus a clinical description (epileptic encephalopathy). There are many early life epilepsies, but ours was the 25th ever described in medical literature.This terminology is now outdated but it may appear on some genetic testing results.
Developmental Epileptic Encephalopathy 25 (DEE25)This name indicates that the disorder is part of a family of genetic disorders that cause both epilepsy and developmental problems. Ours is the 25th such disorder described in the medical literature.DEE25 is the term now used by OMIM. DEE25 replaced the older term EIEE25. It is used by healthcare professionals and may appear on genetic testing results.
Kohlschutter-Tonz Syndrome (non-ROGDI)This name combines the last names of 2 doctors who described a syndrome based on clinical presentation prior to a time when genetic testing was available.Once genetic testing became available, researchers discovered that Kohlschutter-Tonz Syndrome was at least 2 separate and unrelated genetic disorders (SLC13A5 and ROGDI) that happen to have similar clinical features.
NaCTThis is the atomic symbol for the name of the protein: sodium (Na) coupled with citrate transport.Basic Scientists.
IndyThis is an acronym for “I’m Not Dead Yet” because the fly model of this disorder lives longer than the typical research fly.Basic Scientists, especially fly researchers.
mIndyThis stands for mammalian Indy. Basic Scientists.

Symptoms

SLC13A5 Epilepsy is a rare form of intractable epilepsy that begins in infancy and proceeds with accumulating disability that significantly impacts individuals throughout their lifetime. Seizures begin shortly after birth and may persist throughout life, although some families are able to control the seizures with seizure medications, especially later in life. Common symptoms associated with SLC13A5 Epilepsy include:

  • Frequent seizures (up to 100s daily)
  • Prolonged seizures (lasting minutes or hours)
  • Movement and balance problems
  • Behavioral and developmental delays
  • Severe difficulty with speech production with better ability to understand language
  • Sleeping difficulties
  • Eating difficulties

Children and adults with SLC13A5 Epilepsy often need help with the following:

  • Bowel, bladder care
  • Feeding
  • Dressing
  • Ambulation
  • Moving in/out of bed
  • Bathing, oral hygiene, grooming
  • Accompaniment to Medical Appointments
  • Protective supervision

For a full list of symptoms, please see Get Diagnosed.

Treatments

At this time, there are no specific treatments that cure the disease. Current treatment options are limited and include:

  • seizure medications
  • physical therapy
  • occupational therapy
  • speech therapy
  • sometimes placement of feeding tubes

The constant care required for someone suffering from SLC13A5 Epilepsy can severely impact the entire family’s quality of life. Early diagnosis enables early treatment, which may improve seizure control.

SLC13A5 Epilepsy is a spectrum disorder, meaning that even affected siblings may present with a wide range of symptom severity and seizure types. Patients respond to seizure and movement treatments differently, which means there is no single treatment we can recommend at this time. However, based on parent report and peer-reviewed publications, there are a handful of treatments that seem to be more effective for SLC13A5 Epilepsy (referred to below as “Best Bet Treatments”) and some treatments may worsen seizures and movement symptoms (referred to below as “Proceed with Close Monitoring”). Seizure medications need to be taken daily and often a combination of several medications will be prescribed simultaneously (polytherapy).

Best Bet Treatments:

  • phenobarbital
  • valproic acid

Additional Treatment Options:

  • acetazolamide
  • benzodiazepines
  • clobazam
  • levetiracetam

Proceed with Close Monitoring:

  • ketogenic diet
  • triheptanoin
  • zinc
  • citrate

We would like to hear if anyone else has had any improvement with any other treatments (info@tessfoundation.org). We recommend that you speak with your neurologist about treatment options for your loved one.

Rescue Treatments

Many patients with SLC13A5 Epilepsy experience prolonged seizures (status epilepticus) that require emergency intervention. Please talk to your doctor about prescribing a rescue medication (e.g., Diastat or Nayzilam). Rescue medications are administered orally, rectally or nasally depending on the medication. They are given as needed in emergencies.

For more information, visit Manage Seizures.

Diagnosis and Inheritance

If both parents are carriers of an abnormal SLC13A5 gene, there is a 1 in 4 chance that their child will have this severe form of epilepsy.

Genes are a blueprint for making proteins. With few exceptions, all people have two copies of every gene. In many cases, the extra copy can act as a “backup” if one of the copies is defective. So far, it appears that both copies of your SLC13A5 gene need to have a change in the DNA sequence in order for you to have SLC13A5 Epilepsy. This means that you must inherit a copy with an abnormal sequence from both your mom and your dad (autosomal recessive inheritance). Because the mom and dad each have a single defective copy of the gene, and they appear healthy, it appears that you only get the disease if you inherit two abnormal copies. These changes are identified through genetic testing which requires a sample of blood or saliva.

For more information about how to get genetic testing, visit Get Diagnosed.

About SLC13A5, a gene responsible for Citrate Transport

Citrate is a small molecule that is found in many types of food and throughout a person’s body. It is an important part of how a cell makes energy. The protein that moves citrate from outside a cell into the inner part of the cell is called a citrate transporter.

In people with seizures and neurologic problems related to the functioning of the citrate transporter, there are changes in the amino acids that make up the transporter protein. The changes in the amino acids are likely to decrease the amount of citrate that is transported into the cell.

However, there are many unanswered questions in children with this disease that need to be addressed to identify appropriate treatment strategies:

  • Why does too little citrate transport cause a person to have seizures and other neurologic problems?
  • Are there specific drugs or supplements that might be tried to treat the disorder?

In order to answer these questions, it is critical to first have patients suffering from a citrate transporter problem appropriately diagnosed and made available for research studies.

On the Horizon

SLC13A5 Epilepsy does not have a cure. However, there are emerging treatments, such as gene replacement therapy and drug repurposing, under development for SLC13A5 Epilepsy.

What is Gene Replacement Therapy?
Gene replacement therapy replaces a faulty gene in an attempt to cure disease or improve your body’s ability to fight disease.

What Gene Therapy is on the horizon for SLC13A5 Epilepsy?
Taysha Gene Therapies has received rare pediatric and orphan drug designation from the FDA and orphan drug designation from the European Commission. This drug was initially developed at UTSW by Rachel Bailey, PhD with funding from TESS Research Foundation.

To learn about other Gene Therapy success stories:
Spinal Muscular Atrophy

Sickle Cell Anemia

What is drug repurposing?
Drug repurposing is the process of finding new uses outside the scope of the original medical indication for existing drugs.

What drug repurposing is on the horizon for SLC13A5 Epilepsy?
TESS Research Foundation continues to fund the development of animal and cellular models of SLC13A5 Epilepsy. To date, we have flies, mice, fish, and patient-derived cellular models of SLC13A5 which we continue to use to screen potential repurposed drugs. Drug repurposing is a time- and cost-effective strategy for rare diseases like SLC13A5 Epilepsy.

Drug repurposing success stories:
The most famous drug repurposing success story is Viagra. Originally developed to treat angina, the drug was repurposed to treat erectile dysfunction. The drug was initially marketed for morning sickness and was repurposed to treat leprosy and multiple sclerosis.