Objective: To investigate the correlation of disease severity in terms of clinical, genetic and molecular parameters in FRDA.

Background: : Friedreich ataxia (FRDA) is a progressive neurodegenerative disease primarily caused by a pathological expansion of a GAA triplet repeat in the FXN gene encoding for the mitochondrial protein frataxin. Human frataxin (FXN) is involved in the mitochondrial biogenesis of iron-sulfur clusters (ISCs). Frataxin deficiency leads to pleiotropic effects, including deregulation of iron homeostasis and increased oxidative stress which contributes to neurodegeneration and subsequently to the major clinical phenotypes.

Method: Clinical symptoms of FRDA are mainly the resultant of genetic severity which arises from repeat expansion of DNA triplets,(GAA ).The relationships between (GAA) with clinical severity (FARS, age of onset, disease duration ), severity of the protein molecule (Frataxin levels), and biochemical parameters (plasma concentration of iron, copper, homocysteine, vitamin B12, cfDNA, cfRNA, cfmiRNA) in FRDA have not been thoroughly investigated. This study, therefore, was conducted to find out the correlation of (GAA) with these elements to predict their role in the course of progression of FRDA. The above stated parameters were determined in 25 FRDA patients. The distribution of these parameters was studied and transformation was used so that data matched the normal distribution closely. Statistical analysis was carried out using the SPSS 14.0 software. All tests were two-tailed and p<0.05 was considered as statistically significant.

Results: An inverse correlation was found between (GAA) repeat length and age of onset (r=-0.523, p = 0.026), frataxin concentration (r = -0.488, p = 0.04), levels of plasma iron (r=-0.347, p = 0.06), plasma cfDNA levels (r=-0.238, p = 0.001), plasma cfmiRNA levels (Pearson correlation coefficient -0.84, p = 0.27). Whereas, significantly positive correlation was found between (GAA) repeat length with duration of disease (r=0.502, p = 0.006), levels of Hcy (r= 0.28, p=0.004) and FARS scores (r=0.475, p = 0.020).

Conclusion: Present findings suggest that the biochemical parameters can be probed as a critical index for the diagnosis and progression of FRDA. The Fe and Hcy levels are important factors to be considered as prognostic markers in FRDA patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-biochemical-and-clinical-findingss-in-friedreichs-ataxia-patients-relationship-with-the-disease-severity/