Differentiating non-epileptic seizures from epileptic seizures in Glut1 deficiency syndrome.

AIM: To investigate the clinical characteristics of non-epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non-epileptic seizures from epileptic seizures. METHOD: This retrospective case-control study included 57 non-epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5-44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. RESULTS: Non-epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye-head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non-epileptic seizures. Providing supplementary food before high-impact exercise or during attacks prevented or mitigated non-epileptic seizures in some individuals. Glut1DS-associated non-epileptic seizures are fundamentally situation-related seizures with specific provoking and ameliorating factors. Non-epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. INTERPRETATION: Non-epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non-epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision-making for acute exacerbation seizures.

Novel compound heterozygous EPG5 mutations consisted with a missense mutation and a microduplication in the exon 1 region identified in a Japanese patient with Vici syndrome.

Vici syndrome is a rare, autosomal recessive, multisystem disorder, characterized by agenesis of the corpus callosum, cataracts, psychomotor delay, cardiomyopathy, hypopigmentation, and recurrent infections. Mutations in the ectopic P-granules autophagy protein 5 homolog gene (EPG5), which encodes a key autophagy regulator, are responsible for this syndrome. A 3-year-old Japanese girl manifesting similar symptoms to those found in patients with Vici syndrome showed intractable diarrhea, rather than immunodeficiency. Whole exome sequencing identified only a heterozygous variant in EPG5, NM_020964.2(EPG5):c.3389A > C (p.His1130Pro), which was inherited from her mother. Sequencing analyses of the EPG5 messenger RNA showed only an altered nucleotide "C" at position, c.3389, indicating decreased expression of the wild-type allele. Microarray-based comparative genomic hybridization revealed a de novo microduplication in the exon 1 region. Large exon deletions and duplications of EPG5 have never been reported so far. This was considered the cause of the decreased expression of the wild-type allele. In conclusion, we successfully identified novel compound heterozygous mutations in EPG5 in a patient who was clinically considered to have Vici syndrome.