SLC13A5 Deficiency

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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 transporter.

In people with seizures, and neurologic problems related to 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 change 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.

Symptoms

Because this is a rare disorder and very few children have been diagnosed with this disease, the full extent of symptoms is yet to be described. However, there are several symptoms that are common in the majority of children diagnosed with SLC13A5 Epilepsy:

Seizures

Seizures beginning within the first few days of life
Multiple seizure types (Short seizure example and Long seizure example)
Refractory to medication

Movement Disorder

Low muscle tone (hypotonia) and a lack of muscle control or coordination of voluntary movements, such as walking or picking up an object (ataxia)
Episodes of body stiffening or weakness lasting a few minutes to a few hours

Developmental Delay

Severe expressive language delay, with better receptive language
Motor delay
Cognitive delay

Biomarkers

Poor development of teeth (hypodontia) or weakness of teeth enamel
Brain MRI that appears normal or has subtle changes in the white matter
EEGs have a relatively well-preserved background for age, even in the face of frequent seizures
Elevated Citrate levels in blood, urine and CSF

The disease phenotype is variable and even siblings with same genetic mutation show differences in the symptoms including type and frequency of seizures, time course of developmental milestones.

Diagnosis

Currently, the way to identify a citrate transporter disorder (SLC13A5 Deficiency) as the cause of a child having intractable seizures is to look at the DNA sequence of the SLC13A5 gene. Only if both the copies of the child’s SLC13A5 genes are mutated, it is considered to be disease causing. For diagnosis, either whole exome sequencing (WES) can be performed OR targeted panel sequencing (SLC13A5 is included in many epilepsy panels) can be performed which is often less expensive and faster to get results.

Here are a few of the companies that can test for SLC13A5 mutations:

- Invitae, United States
- Centogene AG-the rare Disease Company, Germany
- GeneDx, United States
- Prevention Genetics, United States
- Genetic Services Laboratory, University of Chicago
- Blueprint Genetics, Finland & United States (Insurance billing and financial assistance programs may be available. Contact the lab to learn about the options)
- Medizinisch Genetisches Zentrum München MGZ München, Germany
- Asper Biotech ltd, Estonia
- Fulgent Genetics, United States
- Ambry Genetics, United States
- CGC Genetics, Portugal
- Greenwood Genetic Center Diagnostic Laboratories, United States
- VU University medical center metabolic Unite, Netherland

So far it appears that you need to have a change in the DNA sequence of both copies of the SLC13A5 genes. This means that you might inherit a copy with an abnormal sequence from both your mother and your father. Because mom and dad have a single copy of the gene that is abnormal, and they seem well, it appears that you only get the disease when you have two abnormal copies.

Treatments

At this time, there are no specific treatments that cure the disease. Treating seizures in children with citrate transporter disorder has proven difficult in some patients. Multiple seizure drugs including acetazolamide and ketogenic diet have been tried with mixed efficacy to manage symptoms of SLC13A5 Deficiency. Several children with SLC13A5 Deficiency participated in a trial of triheptanoin with not much success. There is anecdotal evidence for informal trials of TCA cycle intermediates and supplements including magnesium and zinc. We would like to hear if anyone else has had any improvement with any other treatments. We recommend that you speak with your neurologist about treatment options for your child.

Printable SLC13A5 Fact Sheets

Patient Family Fact Sheet

Research Professional Fact Sheet