Medicine:SLC13A5 citrate transporter disorder
SLC13A5 Epilepsy is a rare genetic spectrum disorder that presents with neurological symptoms. Symptoms include severe seizures, ataxia, dystonia, teeth hypoplasia, poor communication skills, difficulty standing or walking, as well as developmental delay. Other names associated with SLC13A5 Epilepsy include SLC13A5 Citrate Transporter Disorder, Citrate Transporter Disorder, SLC13A5 Deficiency, Early Infantile Epilepsy Encephalopathy 25 (EIEE25), Developmental Epilepsy Encephalopathy 25 (DEE25), and Kohlschutter-Tonz Syndrome (non-ROGDI).
SLC13A5 Epilepsy is due to lack of function of the SLC13A5 gene, typically due to inherited mutations in both copies of SLC13A5. This disorder follows autosomal recessive inheritance patterns. Diagnosis is suspected based on symptoms and confirmed by genetic testing.
Individuals with SLC13A5 Epilepsy require an accurate diagnosis to receive proper treatment, particularly with the precision therapy in development for this disease. Proper diagnosis and care are critical, as these patients are dependent upon caregivers throughout their lives.
Genetics
Mutation in the SLC13A5 gene can cause neonatal seizures in the first few days of life.[1] 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.[2] It was discovered in 2002 that it binds preferentially to and transports citrate anions.[3] It is known as Na+-coupled citrate transporter (NaCT), and is also referred to by the gene name SLC13A5.[4]
Citrate deficiency
The disorder is caused by loss of function 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.[5]
Diagnosis
SLC13A5 disorder is an autosomal recessive disease, and its genetic diagnosis can be carried out by exome sequencing. 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.[6]
Treatment
Results on ketogenic diet and drug treatment with triheptanoin are unclear.[6] In 2021 Taysha Gene Therapies announced recognition for their TSHA-105 gene therapy as an orphan drug, by the FDA and European Commission.[7][8]
Support Organizations
TESS Research Foundation is an international organization dedicated to improving the lives of those affected by SLC13A5 Epilepsy by connecting families, clinicians, and researchers. The foundation funds research, provides support to both patients and families, and increases awareness about SLC13A5 Epilepsy. If you’d like to learn more about SLC13A5 Epilepsy, hear from affected families, or get involved with the TESS Research Foundation, you can visit their website and get connected.
Notes
- ↑ Firth, Helen V.; Hurst, Jane A. (2017) (in en). Oxford Desk Reference: Clinical Genetics and Genomics. Oxford University Press. p. 410. ISBN 978-0-19-955750-9. https://books.google.com/books?id=c4c0DwAAQBAJ&pg=PA410.
- ↑ "SLC13A5 solute carrier family 13 member 5 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/284111.
- ↑ "*608305 - SOLUTE CARRIER FAMILY 13 (SODIUM-DEPENDENT CITRATE TRANSPORTER), MEMBER 5; SLC13A5" (in en-us). https://www.omim.org/entry/608305.
- ↑ Ganapathy, Vadivel; Mycielska, Maria E.; Parkinson, Eric Kenneth; Haferkamp, Sebastian (12 August 2022) (in en). Metabolite and Nutrient Transporters in Cancer-Cell Metabolism: Role in Cancer Progression and Metastasis. Frontiers Media SA. p. 56. ISBN 978-2-88976-768-7. https://books.google.com/books?id=d9uAEAAAQBAJ&pg=PA56.
- ↑ Ozlu, C; Bailey, RM; Sinnett, S; Goodspeed, KD (2021). "Gene Transfer Therapy for Neurodevelopmental Disorders.". Developmental Neuroscience 43 (3–4): 234–235. doi:10.1159/000515434. PMID 33882495.
- ↑ 6.0 6.1 "SLC13A5 Citrate Transporter Disorder". https://rarediseases.org/rare-diseases/slc13a5-epileptic-encephalopathy/.
- ↑ "Taysha Gene Therapies Receives Rare Pediatric Disease and Orphan Drug Designations". https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-receives-rare-pediatric-disease-and-0.
- ↑ "Taysha Gene Therapies Receives Orphan Drug Designation". https://ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-receives-orphan-drug-designation-tsha-105.
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