Mitochondrial disorders - investigations 

Definitive investigations have become more complex and specialized. However, clinical clues can point towards a mitochondrial disorder and fairly simple tests support the diagnosis sufficiently to proceed to specific investigations of mitochondrial function.

To a certain extent there is a relationship between the type of disease and the site of metabolic defect along the pathway from the inner mitochondrial membrane to the termination of the respiratory chain, but there is considerable heterogeneity.

It has long been known that most of the genes responsible for mitochondrial function are nuclear rather than mitochondrial genes, and recently some of these nuclear genes have become much more accessible to analysis. The most important of these is POLG or POLG1, that is, mitochondrial DNA polymerase-gamma.

A major way by which mutations in POLG1 affect mitochondrial function is by inducing mitochondrial depletion. Such mitochondrial depletion may be either generalized or organ specific. Other genes of recent interest include Twinkle, DGUOK and the gene for thymidine kinase 2.