SLC13A5 Цитральное транспортер расстройство транспортера
SLC13A5 Цитральное расстройство транспортера цитрата , или эпилепсия SLC13A5 , представляет собой редкое расстройство генетического спектра , которое имеет неврологические симптомы. Симптомы включают тяжелые припадки , атаксию , дистонию , гипоплазию зубов, плохие навыки общения, трудности с стоянием или ходьбой, а также задержку развития . [ 1 ] Другие имена, связанные с эпилепсией SLC13A5, включают в себя расстройство транспортера цитрата SLC13A5, расстройство цитрата транспортер, дефицит SLC13A5, ранняя инфантная эпилепсия энцефалопатия 25 (EIEE25), энцефалопатия эпилепсии развития 25 (DEE25) и Kohlschutter-tonz-sincrome (Non-ROGDM (NON-ROGDI (NON-ROGDI (NON-ROGDM (NON-ROGDM (NON-ROGDM (NON-ROGDM (DEE25) и KOHLSCHUTTER-TONZ-TonZ-TonZ-TonZ-Tonz-Ton [ 2 ]
Эпилепсия SLC13A5 обусловлена дисфункцией гена SLC13A5 , обычно из -за наследственных мутаций в обеих копиях SLC13A5 . Это расстройство следует за аутосомно -рецессивным схемами наследования. [ 3 ] Диагноз подозревается на основе симптомов и подтверждается генетическим тестированием.
Люди с эпилепсией SLC13A5 требуют точного диагноза для получения надлежащего лечения, особенно с точной терапией в развитии этого заболевания. Правильный диагноз и уход имеют решающее значение, так как эти пациенты зависят от лиц, осуществляющих уход, на протяжении всей своей жизни.
Признаки и симптомы
[ редактировать ]Наиболее распространенными симптомами эпилепсии SLC13A5 являются судороги, отсроченное неврологическое развитие и значительные дефекты в развитии зубов. [ 4 ] Другие симптомы включают атаксию, дистонию, глобальную задержку развития и инвалидность. [ 4 ] Люди с эпилепсией SLC13A5 имеют широко распределенные зубы, но без диссморфизма лица нет. [ 1 ]
Nervous System
[edit]People with SLC13A5 Epilepsy present with severe, convulsive multi-focal seizures leading to status epilepticus within the first few weeks of life.[1][3][4] They continue to have seizures of varying type (focal, multi-focal, generalized, tonic-clonic, etc), frequency, and severity for the rest of their lives.[1] Unfortunately, these seizures are poorly controlled by medications.
People with SLC13A5 Epilepsy also experience combinations of spasticity, dystonia (involuntary contraction of muscles), ataxia (poor motor coordination), and choreoathetosis (involuntary twitching or writhing).[1][4]
Dental and Oral
[edit]People with SLC13A5 Epilepsy often have enamel hypoplasia, leading to widely spaced teeth, teeth hypoplasia, hypodontia, and gingival hyperplasia.[1]
Development
[edit]People with SLC13A5 Epilepsy present with varying degrees of developmental delay.[1][3][4] Developmental delay is often obvious by 6 months of age, with lack of rolling, inability to demonstrate head support, and poor eye contact. Walking without support and speech onset are also delayed. People with SLC13A5 Epilepsy also present with varying levels of intellectual disability and limited ability to speak.
Genetic basis
[edit]Mutation in the SLC13A5 gene can cause neonatal seizures in the first few days of life.[5] 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.[6] It was discovered in 2002 that it binds preferentially to and transports citrate anions.[7] It is known as Na+-coupled citrate transporter (NaCT), and is also referred to by the gene name SLC13A5.[8]
Citrate deficiency
[edit]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.[9]
Diagnosis
[edit]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.[2]
Treatment
[edit]Results on ketogenic diet and drug treatment with triheptanoin are unclear.[2] In 2021 Taysha Gene Therapies announced recognition for their TSHA-105 gene therapy as an orphan drug, by the FDA and European Commission.[10][11]
Notes
[edit]- ^ Jump up to: a b c d e f g Goodspeed, Kimberly; Liu, Judy S.; Nye, Kimberly L.; Prasad, Suyash; Sadhu, Chanchal; Tavakkoli, Fatemeh; Bilder, Deborah A.; Minassian, Berge A.; Bailey, Rachel M. (2022-09-15). "SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy". Genes. 13 (9): 1655. doi:10.3390/genes13091655. ISSN 2073-4425. PMC 9498415. PMID 36140822.
- ^ Jump up to: a b c "SLC13A5 Citrate Transporter Disorder". NORD (National Organization for Rare Disorders).
- ^ Jump up to: a b c Whitney, Robyn; Choi, Elaine; Jones, Kevin C. (March 2023). "The neuroimaging spectrum of SLC13A5 related developmental and epileptic encephalopathy". Seizure. 106: 8–13. doi:10.1016/j.seizure.2023.01.014. PMID 36701889. S2CID 256107491.
- ^ Jump up to: a b c d e Matricardi, Sara; De Liso, Paola; Freri, Elena; Costa, Paola; Castellotti, Barbara; Magri, Stefania; Gellera, Cinzia; Granata, Tiziana; Musante, Luciana; Lesca, Gaetan; Oertel, Julie; Craiu, Dana; Hammer, Trine B.; Møller, Rikke S.; Barisic, Nina (November 2020). "Neonatal developmental and epileptic encephalopathy due to autosomal recessive variants in SLC13A5 gene". Epilepsia. 61 (11): 2474–2485. doi:10.1111/epi.16699. ISSN 0013-9580. PMID 33063863.
- ^ Firth, Helen V.; Hurst, Jane A. (2017). Oxford Desk Reference: Clinical Genetics and Genomics. Oxford University Press. p. 410. ISBN 978-0-19-955750-9.
- ^ "SLC13A5 solute carrier family 13 member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
- ^ "*608305 – Solute Carrier Family 13 (Sodium-Dependent Citrate Transporter), Member 5; SLC13A5". www.omim.org.
- ^ Ganapathy, Vadivel; Mycielska, Maria E.; Parkinson, Eric Kenneth; Haferkamp, Sebastian (12 August 2022). 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.
- ^ 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. S2CID 234815220.
- ^ "Taysha Gene Therapies Receives Rare Pediatric Disease and Orphan Drug Designations". ir.tayshagtx.com.
- ^ "Taysha Gene Therapies Receives Orphan Drug Designation". ir.tayshagtx.com.