Complex Disease/Deficiency (Overview)

The mitochondrial myopathies are a rare group of conditions affecting the respiratory chain and oxidative phosphorylation. A total of five protein complexes make up the mitochondrial electron transport chain. The clinical consequences of a deficiency in their normal physiology is associated with numerous syndromes as described in this section and presented in this book. Because of the complexity of this group of diseases, an overview is presented here, followed by a short description of the five individual deficiencies. Table C-2 lists the names of the associated medical disorders that are described as specific syndromes in this book.

(Figure)

“Mitochondrial medicine” was defined by Luft and Moyan-Hughes in the late 1980s and became the subject of numerous investigations of the metabolic disorders affecting the muscles and the brain. Mitochondria were first recognized in 1898 by Bend. The term comes from the Greek mitos (thread) and chondros (grain). The concept of cellular respiration was defined and studied in the 1920s.

In the 1970s and mid-1980s, the standard classification of respiratory chain disorders rested on the biochemical phenotype; however, this approach for mitochondrial DNA (mtDNA) mutations leading to respiratory inefficiencies is now less clear. It is accepted that most mtDNA mutations affect the subunit synthesis either through a mutation in a key tRNA (transfer RNA) gene or through deletion of a series of tRNA genes. The presence of tRNA mutations may, among other mechanisms, lead to amino acid dysfunction most probably within larger subunits.

See Tables C-2 and C-3.