SLC13A5 citrate transporter disorder is a rare neurological disease, also known as SLC13A5 epilepsy and by other names. It is a

spectrum disorder A spectrum disorder is a mental disorder that includes a range of linked conditions, sometimes also extending to include singular symptoms and traits. The different elements of a spectrum either have a similar appearance or are thought to be cause ...

, discovered in 2014. It is one of the many subtypes of

Ohtahara syndrome Ohtahara syndrome (OS), also known as early infantile epileptic encephalopathy (EIEE) is a progressive epileptic encephalopathy. The syndrome is outwardly characterized by tonic spasms and partial seizures within the first few months of life, and ...

(early infantile epileptic encephalopathy or EIEE) that have been linked to metabolic causes.

Genetic basis

Mutation in the

SLC13A5 Solute carrier family 13 (sodium-dependent citrate transporter), member 5 also known as the Na+/citrate cotransporter or mIndy is a protein that in humans is encoded by the SLC13A5 gene. It is the mammalian homolog of the fly Indy gene. Functio ...

gene can cause

neonatal seizure A neonatal seizure is a seizure in a baby younger than age 4-weeks that is identifiable by an electrical recording of the brain. It is an occurrence of abnormal, paroxysmal, and persistent ictal rhythm with an amplitude of 2 microvolts in the elec ...

s in the first few days of life. This condition is known as early infantile epileptic encephalopathy 25. The protein encoded by the gene belongs to a solute carrier family, numbered as 13. It was discovered in 2002 that it binds preferentially to and transports citrate anions. It is known as Na⁺-coupled citrate transporter (NaCT), and is also referred to by the gene name SLC13A5.

Citrate deficiency

The disorder is caused by

loss of function In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...

mutations in the SLC13A5 gene, with impact on citrate transport into cells. Patients typically suffer seizures in the first week of life, and develop a form of

drug-resistant epilepsy Drug-resistant epilepsy (DRE), also known as refractory epilepsy or pharmacoresistant epilepsy, is diagnosed when there failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs (AEDs) (whether as monotherapi ...

Diagnosis

SLC13A5 disorder is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

disease, and its genetic diagnosis can be carried out by

exome sequencing Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome (known as the exome). It consists of two steps: the first step is to select only the subse ...

. The cause is biallelic loss of function, or in other words the disorder occurs when each of the two copies of the gene in the patient is mutated. For practical reasons sequencing of an epilepsy-related panel of genes may replace analysis of the whole exome.

Treatment

Results on

ketogenic diet The ketogenic diet is a high- fat, adequate-protein, low-carbohydrate dietary therapy that in conventional medicine is used mainly to treat hard-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than ca ...

and drug treatment with

triheptanoin Triheptanoin, sold under the brand name Dojolvi, is a medication for the treatment of children and adults with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). The most common adverse reactions include abdominal pain, d ...

are unclear. In 2021 Taysha Gene Therapies announced recognition for their TSHA-105

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

as an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

, by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

and

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

Notes

{{reflist Rare diseases Neurological disorders Epilepsy types