SLC13A5 citrate transporter disorder epilepsy phenotype.

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Loss-of-function variants in the SLC13A5 gene cause autosomal recessive developmental and epileptic encephalopathy 25 (DEE25).
• DEE25 is an ultra-rare genetic disorder characterized by neonatal onset epilepsy, neurocognitive, and motor impairments.

Purpose of the Study:

• To characterize the epilepsy phenotype in children and adults with DEE25.
• To assess seizure burden, antiseizure medication (ASM) efficacy, quality of life, and EEG findings over a 2-year prospective study.

Main Methods:

• Prospective natural history study involving 30 children and adults with DEE25.
• Data collection included seizure frequency, emergency room visits, ASM use and efficacy, quality of life assessments, and EEG analysis over 2 years.

Main Results:

• Seizure burden and ER visits were highest in the first decade of life, decreasing but persisting after age 10.
• Valproic acid was the most utilized ASM, with 80% of caregivers reporting benefit; higher doses correlated with improved outcomes.
• Quality of life scores were low and stable, with cognitive and executive functions more impaired than mood and behavior. Most EEGs were abnormal, but interictal epileptiform activity was not consistently abundant.

Conclusions:

• While seizure burden may decrease after childhood, individuals with DEE25 experience persistent epilepsy risks and low quality of life.
• Valproic acid shows promise as an effective ASM for DEE25, though further research is needed.
• Interictal epileptiform activity on EEG may not be the primary driver of neurocognitive dysfunction in DEE25.