WARS2 -Associated Neuropsychiatric Phenotype in Childhood: A Case-Based Review

Area of Science:

• Neurology
• Genetics
• Mitochondrial Biology

Background:

• Mitochondrial WARS2-related disorders manifest with a wide range of neurological symptoms, including epilepsy and movement disorders.
• The WARS2 gene encodes a mitochondrial tryptophanyl-tRNA synthetase, crucial for protein synthesis within mitochondria.

Purpose of the Study:

• To report a rare case of WARS2-related disorder in an 11-year-old male presenting with movement and behavioral issues.
• To characterize the genetic mutation and clinical phenotype.
• To document the treatment response in this specific patient.

Main Methods:

• Clinical case presentation and detailed neurological examination.
• Genetic analysis, including whole exome sequencing or targeted gene sequencing, to identify mutations in the WARS2 gene.
• Assessment of clinical response to levodopa therapy.

Main Results:

• The patient presented with tremors, dystonic falls, social anxiety, and impulse control disorder (ICD) with symptom onset at age 6.
• Genetic analysis identified a compound heterozygous mutation in the WARS2 gene (p.Thr154ProfsTer66 in exon 4 and p.Trp13Gly in exon 1).
• The patient showed a significant clinical improvement after treatment with levodopa.

Conclusions:

• This case represents the first reported instance of a WARS2-related disorder in India.
• The findings expand the known phenotypic spectrum of WARS2-related disorders.
• Levodopa may be an effective therapeutic option for certain WARS2-related movement and behavioral symptoms.