Genotype-driven therapeutics in DEE and metabolic epilepsy: navigating treatment efficacy and drug resistance.

Autor: Nguyen YTM; Department of Biotechnology, International University, Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam.; Unit of AI Genomics, DNA Medical Technology, Ho Chi Minh City, Vietnam., Vu BQ; Institute of Food and Biotechnology, Can Tho University, Can Tho City, Vietnam.; Faculty of Computer Science, University of Information Technology, Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam., Nguyen DK; Department of Neurology, City Children's Hospital, Ho Chi Minh City, Vietnam., Quach NV; Department of Neurology, City Children's Hospital, Ho Chi Minh City, Vietnam., Bui LT; Institute of Food and Biotechnology, Can Tho University, Can Tho City, Vietnam., Hong J; Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.; HnB Genomics, Ulsan, South Korea., Bui CB; University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh, Vietnam. bcbao@medvnu.edu.vn.; Unit of Molecular Biology, City Children's Hospital, Ho Chi Minh City, Vietnam. bcbao@medvnu.edu.vn.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 16; Vol. 14 (1), pp. 21606. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1038/s41598-024-72683-7
Abstrakt: Neonatal intensive care unit (NICU), particularly in treating developmental and epileptic encephalopathy (DEE) and metabolic epilepsy (ME), requires a deep understanding of their complex etiologies and treatment responses. After excluding treatable cases such as infectious or autoimmune encephalitis, our focus shifted to a more challenging subgroup of 59 patients for in-depth genetic analysis using exome sequencing (ES). The ES analysis identified 40 genetic abnormalities, significantly including de novo variants. Notably, we found structural variation as duplications in regions 2q24.3, including SCN1A and SCN2A were observed in 7 cases. These genetic variants, impacting ion channels, glucose transport, transcription regulation, and kinases, play a crucial role in determining medication efficacy. More than one-third (34.2%) of patients with DEE had an unfavorable response to anti-seizure medications (ASMs) in the chronic phase. However, since the ketogenic supplementary diet showed a positive effect, more than three-quarters (80%) of these drug-resistant patients improved during a 3-month follow-up. In contrast, the ME had a lower adverse reaction rate of 9.1% (2/22) to specialized medications, yet there were 5 fatalities and 10 cases with unidentified genetic etiologies. This study suggests the potential of categorizing drug-resistant variants and that a ketogenic diet could be beneficial in managing DEE and ME. It also opens new perspectives on the mechanisms of the ketogenic diet on the discovered genetic variants.
(© 2024. The Author(s).)
Databáze: MEDLINE
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