Resumo

NOGUEIRA, Célia et al. Nuclear-mitochondrial intergenomic communication disorders: clinical and laboratory approach. Arq Med [online]. 2015, vol.29, n.1, pp.11-19. ISSN 2183-2447.

Mitochondrial dysfunction accounts for an important and heterogeneous group of inherited metabolic disorders with hitherto no effective therapeutic options. most of the known mitochondrial disorders are caused primarily by a dysfunctional oxidative phosphorylation and consequently a deficient energy production. This system depends on the coordinated expression of both nuclear and mitochondrial genomes. Therefore, mitochondrial diseases can be caused by genetic defects in the mitochondrial or the nuclear genome or in the interplay between the two genomes, causing nuclear-mitochondrial intergenomic communication disorders. The mitonuclear crosstalk has gained increased relevance in the past years and since then many genes have been identified as being involved in these diseases. Nuclear-mitochondrial intergenomic communication disorders can be divided into two distinct groups: i) multiple deletions syndrome, leading to qualitative changes of mtDNA, that occurs in adults, having as main clinical features ocular and limb myopathy, which are almost always associated with extramuscular system involvement or ii) depletion syndrome, leading to quantitative changes of mtDNA, occurring in infancy or early childhood further subdivided into three clinical categories: myopathic, encephalomyopathic and hepatocerebral. The focus of this review is to provide an overview of intergenomic communication disorders, a list of clinical phenotypes accompanied by their mutational spectrum and a diagnostic algorithm, which can be useful for clinicians when facing similar cases.

Palavras-chave : mitochondrial DNA depletion; mitochondrial DNA multiple deletions; mitochondrial diseases; intergenomic communication disorders.

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