Friedreich’s ataxia is caused by a genetic mutation that affects the production of a critical protein called frataxin, which is essential for the proper functioning of mitochondria—the energy-producing structures inside cells. The root cause lies in a specific gene known as the FXN gene, located on chromosome 9. In most cases, this gene contains an abnormal expansion of a DNA sequence made up of three nucleotides—guanine (G), adenine (A), and adenine (A)—repeated many times in a row. This is called a GAA trinucleotide repeat expansion.
Normally, the FXN gene produces frataxin at levels sufficient to maintain healthy mitochondrial function. However, when the GAA repeats expand beyond a certain threshold—ranging from about 90 to over 1,300 repeats—this causes the DNA around the gene to become tightly packed into a form called heterochromatin. This tightly packed DNA structure suppresses the gene’s activity, leading to a significant reduction in frataxin production. People with Friedreich’s ataxia typically have only 5 to 35 percent of the normal frataxin levels in their cells.
Frataxin plays a vital role in managing iron within mitochondria and in the assembly of iron-sulfur clusters, which are essential components for many enzymes involved in energy production and protecting cells from oxidative damage. When frataxin is deficient, iron accumulates abnormally inside mitochondria, causing oxidative stress and damage
