Dados do Trabalho

Título

NEURODEVELOPMENTAL DISORDER WITH INVOLUNTARY MOVEMENTS ASSOCIATED WITH THE WARS2 GENE IN INFANT: A CASE REPORT.

Apresentação do caso

CASE: A 15-month-old girl evolved with fever and tremors associated with ataxy after vaccination of hepatitis A, DTP, OPV y tetraviral. She was born via cesarean, uneventfully. Parents are consanguineous. Her mother had Specific Hypertensive Pregnancy Disease (SHPD) during pregnancy. No history of previous hospitalizations, regular medications, and allergies. Neuropsychomotor development (NPMD): she sat at 6 months, babbles and waves, and didn’t walk but stood with support by 12 months. The cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and cerebral spinal fluid were normal. Diagnostic hypothesis: acute cerebellitis. An intravenous combination of ceftriaxone and acyclovir was given for 10 days, evolving with an improvement in tremors. It was prescribed clonazepam for ambulatorial use. After 3 months, the fever began again, getting worse the tremors and ataxia. Physical exam: without trunk support; decreased muscle strength in lower and upper limbs (LL. and UP.), with hypertonia, reflexes, and distal clonus in LL.; tongue and chin tremors. Genetic analysis, Next Generation Sequencing (NGS), by Movimente Program, identified compound homozygous mutations in the WARS2 gene, being the paternally inherited missense variant: c.754C>T, (p.Arg252Cys) with uncertain significance.

Discussão

Protein translation is critical for all forms of life, and aminoacyl transfer RNA (tRNA) synthetases (ARSs) play an important role in this process. ARSs ensure the incorporation of correct amino acids in the growing polypeptide chain during protein synthesis. Each protein-genic amino acid is coupled to its corresponding tRNA by a specific ARS. Mitochondrial ARSs are encoded by separate nuclear genes and an increasing proportion of ARS genes has been associated with human disease. WARS2 is a mitochondria-specific AR named tryptophanyl-RNA synthetase 2 and its deficiency can cause heterogeneous clinical presentations (e.g., muscle weakness, peripheral neuropathy, movement disorder, epilepsy), but developmental cognitive delay and complex movement disorders are prevalent mark, and the absence of epileptic seizures can increase patient survival. NGS techniques became widely available and, are a powerful tool to unravel the heterogenic genetic background of MD.

Comentários finais

CONCLUSION: In children with otherwise unexplained progressive hyperkinetic movement disorders, WARS2-related mitochondrial disease should be included in the list of differential diagnoses.

Referências (se houver)

ANTONELLIS, Anthony; GREEN, Eric D. The role of aminoacyl-tRNA synthetases in genetic diseases. Annu. Rev. Genomics Hum. Genet., v. 9, p. 87-107, 2008.
FUCHS, S. A. et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genetics in Medicine, v. 21, n. 2, p. 319–330, 2019.
SCHAEFER, Andrew M. et al. The epidemiology of mitochondrial disorders—past, present and future. Biochimica et Biophysica Acta (BBA)-Bioenergetics, v. 1659, n. 2-3, p. 115-120, 2004.
MUNNICH, A. et al. Clinical presentation of mitochondrial disorders in childhood. Journal of inherited metabolic disease, v. 19, n. 4, p. 521-527, 1996
WORTMANN, Saskia B. et al. Whole exome sequencing of suspected mitochondrial patients in clinical practice. Journal of inherited metabolic disease, v. 38, n. 3, p. 437-443, 2015.
HÜBERS, A. et al. Mutation of the WARS2 Gene as the Cause of a Severe Hyperkinetic Movement Disorder. Movement Disorders Clinical Practice, v. 7, n. 1, p. 88–90, 2020.

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