Mitochondrial diseases are, as a group, the most common inherited metabolic disorders and the most frequent inherited disorders at the neurological level.
They are clinically heterogeneous, can occur at any age, and usually can produce a wide range of clinical symptoms, being often considered multisystem diseases. Some mitochondrial diseases can be grouped into specific syndromes, such as Leigh syndrome (infantile subacute necrotizing encephalomyopathy), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), or Alpers-Huttenlocher syndrome. In addition to biochemical and histochemical analysis of tissue biopsy samples, diagnosis is usually based on clinical criteria. Not only does genetic testing contribute to better clinical and molecular characterization of these patients, it also helps provide appropriate genetic counseling for the individual and their family.
The prevalence of mitochondrial diseases that begin in childhood is between 5-15 per 100,000 individuals (Gorman et al., 2014). The most common presentation is Leigh syndrome (2.5 per 100,000 individuals). An estimated prevalence in adults is 9.6 per 100,000 (due to mtDNA mutations) and 2.9 per 100,000 individuals (caused by mutations in nuclear genes).
Mitochondrial defects can result from mutations in nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) genes. With regard to genetic suspicion, it is worth mentioning that 80% of adult-onset mitochondrial diseases are due to pathogenic variants in mtDNA; however, they only account for 20-25% of childhood-onset cases, where nuclear genes are more important (Gorman et al., 2014).