Case Studies in Neuroscience: A Novel Amino Acid Duplication in the N-terminus of the Brain Sodium Channel NaV1.1 Underlying Dravet Syndrome.
Journal of neurophysiology
Plasma taurine levels are not affected by vigabatrin in pediatric patients.
2016; 57 (8): e168-72
Dravet syndrome is a severe form of childhood epilepsy characterized by frequent temperature-sensitive seizures and delays in cognitive development. In the majority (80%) of cases, Dravet Syndrome is caused by mutations in the SCN1A gene, encoding the voltage-gated sodium channel NaV1.1, which is abundant in the central nervous system. Dravet syndrome can be caused by either gain-of-function mutation or loss-of-function in NaV1.1, making it necessary to characterize each novel mutation. Here we use a combination of patch-clamp recordings and immunocytochemistry to characterize the first known N-terminal amino acid duplication mutation found in a patient with Dravet Syndrome, M72dup. M72dup does not significantly alter rate of fast inactivation recovery, or rate of fast inactivation onset at any measured membrane potential. M72dup significantly shifts the midpoint of the conductance voltage relationship to more hyperpolarized potentials. Most interestingly, M72dup significantly reduces peak current of NaV1.1 and reduces membrane expression. This suggests that M72dup acts as a loss-of-function mutation primarily by impacting the ability of the channel to localize to the plasma membrane.
View details for DOI 10.1152/jn.00491.2019
View details for PubMedID 31533007
Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children.
View details for DOI 10.1111/epi.13447
View details for PubMedID 27344989