2021 Western Medical Research Conference

2020 Journal of Investigative Medicine  
Purpose of Study To refine the electroclinical phenotype of epilepsy in NGLY1 deficiency via prospective clinical and electroencephalogram (EEG) findings in an international cohort. Methods Used We performed prospective phenotyping of 28 subjects with NGLY1 deficiency via standardized clinician interviews every 4 months of medical, developmental and seizure history. Seizure and medication history was confirmed with prior records. 14 subjects also underwent in-person evaluations including EEG,
more » ... tained via 20 lead standard array. Descriptive statistics are provided for the first year of an ongoing natural history study. Summary of Results All subjects had typical symptoms including: global developmental delay and/or intellectual disability, hypo-or alacrima, hyperkinetic movement disorder and transient elevation in transaminases. 17/28 (60.7%) had a history of epilepsy, with mean seizure onset at 37 months (interquartile range 5-60 months, range 2 months to 19 years). Seizure types included myoclonic (8/17, 47%), astatic (7/17, 41%), and absence (6/17, 35%); focal with secondary generalization, tonic, generalized tonic clonic, and infantile spasms were also reported. 10/14 (71%) subjects had generalized interictal epileptiform activity on EEG. EEG background was otherwise normal without slowing in the majority of subjects. Commonly used antiseizure medications were valproate, levetiracetam, lamotrigine, and clobazam. 7/17 subjects achieved complete seizure control on a variety of medications. Conclusions We highlight a significant risk of epilepsy in NGLY1 deficiency and detail the clinical and electrographic features identified in our international cohort. Seizure semiology is varied, with predominant myoclonic, astatic and absence seizure types with onset most commonly in infancy or early childhood. EEG abnormalities are non-specific and indicate a genetic risk of epilepsy, but most patients do not have EEG slowing which is a correlate of encephalopathy. Seizures often require treatment with multiple medications. Commonly used medications in various combinations include valproate and clobazam, indicating hepatic tolerance of these medications. Providers should educate caregivers about varied seizure types to ensure prompt detection and treatment of epilepsy.
doi:10.1136/jim-2021-wrmc fatcat:ec52pfr2efgafb665m2czugyqy