Neonatal encephalocardiomyopathy caused by mutations in VARS2

Area of Science:

• Genetics
• Neurology
• Mitochondrial Biology

Background:

• VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase, essential for mitochondrial protein synthesis.
• Mutations in VARS2 have been linked to mitochondrial encephalomyopathy, but clinical data is limited.

Observation:

• A boy presented with severe lactic acidosis, hypertrophic cardiomyopathy, epilepsy, and brain abnormalities including corpus callosum and cerebellar hypoplasia.
• Exome sequencing identified compound heterozygous pathogenic VARS2 variants in the patient.

Findings:

• The identified VARS2 variants were confirmed as pathogenic through functional studies in patient-derived fibroblasts.
• The study expands the phenotypic spectrum of VARS2 deficiency, revealing severe neonatal presentations with cardiac and structural brain involvement.

Implications:

• VARS2 deficiency should be considered in neonatal cases with severe lactic acidosis, cardiomyopathy, and neurological deficits.
• This research highlights the critical role of VARS2 in mitochondrial function and overall development.
• Further investigation into mitochondrial disorders associated with VARS2 is warranted.