Mitochondrial disorders are overall the most common group of inherited metabolic diseases, and they are among the most frequent hereditary neurological diseases.
They are clinically heterogeneous, can occur at any age, and generally manifest with a wide array of clinical symptoms, usually being defined as multisystem diseases. Some mitochondrial disorders can be grouped into specific syndromes such as Leigh syndrome (subacute necrotizing encephalomyelopathy), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), or Alpers-Huttenlocher syndrome. Diagnosis is usually based on clinical criteria, as well as on biochemical and histochemical analysis of biopsies. Genetic study contributes to the improved clinical and molecular characterization of these patients and allows providing adequate genetic advice for the individuals and their families.
The prevalence of childhood-onset mitochondrial diseases is 5-15/100 000 individuals (Gorman et al., 2014). The most common form of
presentation is Leigh syndrome (2.5/100 000). The prevalence in adults is estimated in 9.6/100 000 (due to mtDNA mutations) and 2.9/100 000 (due to mutations in nuclear genes).
The mitochondrial defect can be caused by mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes. With regard to genetic suspicion, it is worth noting that 80% of mitochondrial diseases in adults are due to pathogenic variants in mtDNA; however, these variants only account for 20%-25% of childhood-onset cases (in which nuclear genes have a greater importance) (Gorman et al., 2014).
We have developed a selection of specific panels for the study of mitochondrial diseases based on the main biochemical findings, as well as a core panel for the study of nuclear gene-encoded Leigh syndrome, with a comprehensive panel including 174 known genes for mitochondrial diseases.