Glutaminase (GLS) hyperactivity was first described in 2019 in a patient with profound developmental delay and infantile cataract. Here, we describe a 4-year-old boy with GLS hyperactivity due to a de novo heterozygous missense variant in GLS, detected by trio whole exome sequencing. This boy also exhibits developmental delay without dysmorphic features, but does not have cataract. Additionally, he suffers from epilepsy with tonic clonic seizures. In line with the findings in the previously described patient with GLS hyperactivity, in vivo 3 T magnetic resonance spectroscopy (MRS) of the brain revealed an increased glutamate/glutamine ratio. This increased ratio was also found in urine with UPLC-MS/MS, however, inconsistently. This case indicates that the phenotypic spectrum evoked by GLS hyperactivity may include epilepsy. Clarifying this phenotypic spectrum is of importance for the prognosis and identification of these patients. The combination of phenotyping, genetic testing, and metabolic diagnostics with brain MRS and in urine is essential to identify new patients with GLS hyperactivity and to further extend the phenotypic spectrum of this disease.
Keywords: GLS hyperactivity; epilepsy; glutamate; high‐throughput sequencing; phenotypic spectrum.
© 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.