Targeted gene under study:
OMIM 138280
Abstract
Background
Glutaminase (GLS) deficiency is a rare metabolic disorder characterized by significant phenotypic variability, making it challenging to diagnose and understand fully. GLS, a critical enzyme involved in multiple metabolic and signaling pathways, plays a pivotal role in cellular functions, particularly in the brain. Deficiency of this enzyme has been linked to a spectrum of neurological disorders and developmental delay.
* Method
We aimed to consolidate current knowledge about GLS deficiency by analyzing the phenotypic spectrum observed in patients with confirmed pathogenic variants in the GLS gene. We report a case of a patient with two novel variants in GLS previously undescribed and reviewed the existing literature to explore potential genotype-phenotype correlations.
* Results
Our findings indicate that GLS deficiency is likely underdiagnosed due to its progressive, variable symptoms and the challenges associated with detecting genetic variants through conventional sequencing techniques. Despite the broad phenotypic variability observed among patients, our study identified three distinct phenotype groups, each associated with varying severity levels. These groups suggest a potential genotype-phenotype correlation, offering new insights into the underlying mechanisms of this rare disorder.
*Conclusion
This study underscores the importance of considering GLS deficiency in patients with unexplained neurological symptoms and developmental delay. It also highlights the need for further research to refine diagnostic tools and deepen our understanding of the relationship between GLS gene mutations and the resulting clinical manifestations.
Coordinating clinician
Marta SPODENKIEWICZ – contact email: leacosme.kine@gmail.com
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: No
3- Linked to a translational/basic research project: No