WARS2 leukoencephalopathy

Evidence-based neurology checklist on wars2 leukoencephalopathy: Genetics This is caused by bi-allelic mutations in the WARS2 gene The gene encodes mitochondrial tryptophanyl tRNA synthetase (mtTrpRS) The mutation results in NEMMLAS syndrome The transmission is autosomal recessive The mutation is…

Genetics

  • This is caused by bi-allelic mutations in the WARS2 gene
  • The gene encodes mitochondrial tryptophanyl tRNA synthetase (mtTrpRS)
  • The mutation results in NEMMLAS syndrome
  • The transmission is autosomal recessive
  • The mutation is characterised by severe combined respiratory chain deficiency in the liver 
  • Mitochondrial function is normal in muscle and skin fibroblasts
  • It is usually neonatal onset but but it may start later

Clinical features

Investigations

Acronym

References

  1. Virdee M, Swarnalingam E, Kozenko M, Tarnopolsky M, Jones K. Expanding the phenotype: neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) due to WARS2 biallelic variants, encoding mitochondrial tryptophanyl-tRNA synthase. J Child Neurol 2019; 34:778-781.
  2. Wortmann SB, Timal S, Venselaar H, et al. Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy. Hum Mutat 2017; 38:1786-1795.
  3. Theisen BE, Rumyantseva A, Cohen JS, et al. Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy. Am J Med Genet A 2017; 173:2505-2510.
  4. Maffezzini C, Laine I, Dallabona C, et al. Mutations in the mitochondrial tryptophanyl-tRNA synthetase cause growth retardation and progressive leukoencephalopathy. Mol Genet Genomic Med 2019; 7:e654.
  5. Vantroys E, Smet J, Vanlander AV, et al. Severe hepatopathy and neurological deterioration after start of valproate treatment in a 6-year-old child with mitochondrial tryptophanyl-tRNA synthetase deficiency. Orphanet J Rare Dis 2018; 13:80. 
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