Spinocerebellar ataxias due to mitochondrial defects

A number of ataxias have been shown to result from defects in mitochondrial function. The genes responsible for Friedreich ataxia (FRDA) and for X-linked sideroblastic anemia with ataxia are nuclear genes that encode mitochondrial proteins. These genes, which are highly conserved in species as diverse as humans and yeast, play a role in mitochondrial iron metabolism and in the formation of iron-sulfur clusters. Defects in vitamin E metabolism, due to mutations in tocopherol transfer protein (TTP), also result in ataxia. It is hypothesized that the biochemical feature common to these ataxias is increased oxidant damage either through increased oxidants or decreased anti-oxidants.