A second case of glutaminase hyperactivity: Expanding the phenotype with epilepsy
Lynne Rumping,
Petra J. W. Pouwels,
Nicole I. Wolf,
Holger Rehmann,
Mirjam M. C. Wamelink,
Quinten Waisfisz,
Judith J. M. Jans,
Hubertus C. M. T. Prinsen,
Jiddeke M. van deKamp,
Peter M. vanHasselt
Affiliations
Lynne Rumping
Department of Human Genetics Amsterdam UMC Amsterdam the Netherlands
Petra J. W. Pouwels
Department of Radiology and Nuclear Medicine and Amsterdam Neuroscience Amsterdam UMC Amsterdam the Netherlands
Nicole I. Wolf
Department of Child Neurology, Amsterdam Leukodystrophy Center Emma Children's Hospital, Amsterdam UMC Amsterdam the Netherlands
Holger Rehmann
Department of Energy and Biotechnology Flensburg University of Applied Sciences Flensburg Germany
Mirjam M. C. Wamelink
Department of Clinical Chemistry, Metabolic Unit, Amsterdam Gastroenterology Endocrinology Metabolism Amsterdam UMC location Vrije Universiteit Amsterdam the Netherlands
Quinten Waisfisz
Department of Human Genetics Amsterdam UMC Amsterdam the Netherlands
Judith J. M. Jans
Department of Genetics, Section Metabolic Diagnostics UMC Utrecht Utrecht the Netherlands
Hubertus C. M. T. Prinsen
Department of Genetics, Section Metabolic Diagnostics UMC Utrecht Utrecht the Netherlands
Jiddeke M. van deKamp
Department of Human Genetics Amsterdam UMC Amsterdam the Netherlands
Peter M. vanHasselt
Department of Genetics, Section Metabolic Diagnostics UMC Utrecht Utrecht the Netherlands
Abstract 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.