Ketogenic diet-responsive drug-resistant epilepsy in a case of asparagine synthetase deficiency with a novel compound heterozygous missense variant

Altıntaş M., YILDIRIM M., Uçar Ç. İ., KÖSE E., BEKTAŞ Ö., TEBER S.

Clinical Neurology and Neurosurgery, cilt.230, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 230
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.clineuro.2023.107772
  • Dergi Adı: Clinical Neurology and Neurosurgery
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE
  • Anahtar Kelimeler: Asparagine synthetase deficiency, Epilepsy, Ketogenic diet, Treatment, Whole-exome sequencing
  • Ankara Üniversitesi Adresli: Evet

Özet

Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder caused by homozygous or compound heterozygous mutations in the ASNS gene. Most of the patients have early-onset intractable seizures. A 7-year-old boy was first admitted to our clinic with intractable febrile and afebrile seizures that started when he was 6 months old. He had axial hypotonia with spastic quadriparesis, mild facial dysmorphism, and acquired microcephaly at 1 year-old. Metabolic tests showed a borderline-low serum asparagine level. The electroencephalogram demonstrated epileptic discharges with a high incidence of multifocal spike-wave activity. Brain MRI showed mild cerebral atrophy. His seizures continued despite combinations of multiple antiseizure agents. Whole-exome sequencing (WES) revealed a novel compound heterozygous missense variant of the ASNS gene, and the variants were confirmed by Sanger sequencing. He was started on a ketogenic diet at five years and six months of age. In the first month of the ketogenic diet, we observed that the frequency of seizures significantly decreased. He showed a remarkable improvement in seizures and milder improvement in cognitive skills. To our knowledge, our case is the first report describing significant improvement with a ketogenic diet in intractable seizures due to ASNSD.