Abstract

Mitochondrial disease enters the differential diagnosis of a wide range of CNS and PNS presentations. Respiratory chain ATP production is under bigenomic genetic control. Adult mitochondrial diseases are mainly caused by mutations in mitochondrial DNA (mtDNA), and nuclear gene defects usually present with more severe childhood phenotypes. Recently, mutations in certain nuclear genes—for example POLG, MFN2 and OPA1, have been associated with an increasing number of adult-onset phenotypes. Achieving an accurate diagnosis can be complex and requires the coordinated interplay of clinical assessment, muscle histochemistry, muscle respiratory chain enzymology and genetics. Factors influencing the transmission and expression of mtDNA defects are not fully defined, presenting difficulties in calculating accurate recurrence risks for patients. Curative therapy exists for primary coenzyme Q₁₀ deficiency. For certain mtDNA mutations new therapeutic strategies, including resistance training, have the potential to reduce mutant mtDNA load. Allogeneic stem cell transplant may produce benefit in the nuclear recessive mitochondrial disorder mitochondrial neurogastrointestinal encephalomyopathy and should be considered in this nuclear driven multiple mtDNA deletion disorder. Supportive therapies in a multidisciplinary team environment are essential to reduce morbidity and mortality.