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Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant
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Orientador(es)
Resumo(s)
Introduction: Combined oxidative phosphorylation deficiency 20 (COXPD20) is a mitochondrial respiratory chain complex (RC) disorder, caused by disease-causing variants in the VARS2 gene, which encodes a mitochondrial aminoacyl-tRNA synthetase. Here we describe a patient with fatal mitochondrial encephalopathy caused by a homozygous VARS2 gene missense variant.
Case Report: We report the case of a girl, the first child of non-consanguineous and healthy parents, born from an uneventful term pregnancy, who presented, in the neonatal period, major hypotonia and microcephaly. At 4 months of age she showed poor eye contact, nystagmus, global psychomotor development delay and failure to thrive, without dysmorphic features. Focal seizures started at 24 months which evolved to a severe epileptic encephalopathy and finally to super refractory status epilepticus, leading to her death at 28 months of age. Etiologic investigation encompassing metabolic and genetic causes failed to disclose a diagnosis. Post-mortem exome sequencing allowed the identification of a pathogenic variant in VARS2 gene in the homozygous state (c.1100C > T, p.Thr367Ile) in the patient, inherited from her heterozygous parents, leading to the diagnosis of COXPD2.
Conclusion: To the best of our knowledge, this is the fifth case described in the literature of a child with disease-causing variant in VARS2. With this report we expand the knowledge about the phenotype associated with this very rare mitochondrial defect, further emphasizing the use of exome sequencing as a very powerful diagnostic tool.
Descrição
Research report
Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226392/
Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226392/
Palavras-chave
Amino Acyl Exome Sequencing Mitochondrial diseases Mitochondrial Encephalopathy RNA Severe Epileptic Encephalopathy Transfer VARS2 gene Doenças Genéticas
Contexto Educativo
Citação
JIMD Rep. 2018;42:113-119. doi: 10.1007/8904_2018_89. Epub 2018 Feb 25
Editora
Springer/ Society for the Study of Inborn Errors of Metabolism (SSIEM)