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Observational Study
. 2024 Feb;194(2):337-345.
doi: 10.1002/ajmg.a.63418. Epub 2023 Oct 18.

Characterization of seizures and EEG findings in creatine transporter deficiency due to SLC6A8 mutation

Myriam Abdennadher  1 , Sara K Inati  2 , Samar Rahhal  3 , Omar Khan  4 , Luca Bartolini  5 , Audrey Thurm  6 , William Theodore  7 , Judith S Miller  8 , Forbes D Porter  3 , Simona Bianconi  9   10
Affiliations
Observational Study

Characterization of seizures and EEG findings in creatine transporter deficiency due to SLC6A8 mutation

Myriam Abdennadher et al. Am J Med Genet A. 2024 Feb.

Abstract

Seizures occur in up to 59% of boys with creatine transporter deficiency (CTD). While seizure phenotypes have been previously described, electroencephalogram (EEG) findings have only been reported in several case reports. In this prospective observational study, we report seizure characteristics and EEG findings in combination with neurobehavioral and SLC6A8 pathogenic variants in twenty males with CTD. Eighteen study participants (SP) underwent video-EEG, and seven had follow-up EEG recordings. Seizures typically occurred by age of 2 years. Thirteen (65%) had non-febrile seizures, requiring anti-seizure medications in nine. Four had febrile seizures. Seizures were bilateral tonic-clonic in 7 SP and focal impaired awareness in 5 SP; often responding to 1 to 2 antiseizure medications. EEG showed slowing in 5 SP, beta activity in 6 SP, and focal/multifocal, and/or generalized epileptiform activity in 9 SP. Follow-up EEGs in 7 SP showed emergence of epileptiform activity in 1 SP, and increased activity in 2 SP. In conclusion, seizures were frequent in our cohort but tended to respond to antiseizure medications. Longitudinal follow up provided further insight into emergence of seizures and EEG abnormalities soliciting future studies with long term follow up. Biomarkers of epileptogenicity in CTD are needed to predict seizures in this population.

Trial registration: ClinicalTrials.gov NCT02769949.

Keywords: EEG; SLC6A8; creatine; creatine transporter deficiency; epilepsy; seizure.

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Figures

Figure 1:
Figure 1:
Age at the first non-febrile seizure. The figure shows that first non-febrile seizure occurred by the age of 4 years in most participants with CTD.
See this image and copyright information in PMC

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