Diagnosis and management of mitochondrial respiratory chain disorders

Abstract 

Mitochondria are intracellular organelles that are widely distributed and have a central role in metabolic activity. Their principal function is the production of cellular energy in the form of ATP, but they also have many other metabolic functions. ATP is generated by oxidative phosphorylation. This pathway has five complexes (I–V), components of which are encoded by two genomes, nuclear and mitochondrial. Nuclear genes encode most of the polypeptides but 13 are encoded by mitochondrial DNA (mtDNA). This is exclusively maternal in origin. Due to the almost universal dependence on mitochondrial energy production, the clinical manifestations of disorders of the respiratory chain are very wide. They may involve any organ at any age. In childhood, investigation requires careful assessment before proceeding to more specific enzyme assays and molecular genetic studies. There is no curative treatment; management is supportive.

Keywords:  mitochondrial respiratory chain, mitochondrial DNA, Leigh syndrome, MELAS syndrome, Pearson syndrome, lactic acidosis