In a research study entitled “Frataxin levels in peripheral tissue in Friedreich ataxia“, published in the Annals of Clinical and Translational Neurology, researchers looked at the levels of frataxin in the buccal mucosa and blood of Friederich ataxia (FA) patients who were homozygous for the disease and in those who were heterozygous carriers of the disease. FA is a genetic condition with symptoms including an ataxic gait, diabetes, scoliosis and cardiomyopathy. It is an autosomal recessive disease characterized by low levels of a protein known as frataxin in the blood and peripheral tissues.
Researchers observed frataxin levels were decreased in the peripheral tissue of Friedreich ataxia patients but in variable amounts in those who were symptomatic with the disease. According to the team, frataxin blood levels were more consistently decreased when compared to buccal mucosa levels. Also, frataxin levels in these two regions did not change much over the course of an individual’s lifetime but, in some cases, it gradually increased.
There were a number of mutations associated with low frataxin levels, the most common of which is a repeating guanine-adenosine-adenosine mutation (GAA mutation) in the gene for frataxin. However, several other mutations also lead to similar symptoms.
The team observed that in FA patients, 98 percent of cases were due to repeating GAA mutations in frataxin-coding DNA, while 2 percent were due to some other kind of genetic alteration, such as point mutations. Importantly, researchers found that the lower the levels of frataxin in blood and buccal mucosa, the faster the onset of Friederich ataxia. The study also revealed that frataxin levels are more consistent in blood samples than in buccal mucosa samples, which means that blood samples are the best option to accurately measure frataxin in FA patients.
Not all mutations were considered alike: people with a GAA mutation yielded an abnormal frataxin protein while those with point mutations as the underlying cause of their FA made no frataxin and therefore had a more severe form of the disease.
These results may lead to improved ways of diagnosing FA while looking for medications that could raise frataxin levels and thus treat the disease.