Objective: Friedreich Ataxia (FRDA) is an inherited recessive disease with reduced frataxin levels. This causes a reduced mitochondrial function and progressive neurodegeneration. The aim of this study is to assess the role of Uric Acid (UA) in this phenomenon.

Background: UA is a scavenger of oxygen radicals, and, because of its the antioxidant capacity, may play a protective role in aging and neurodegeneration. Although hyperuricemia is associated with metabolic syndrome and stroke, higher serum UA levels have been linked to decreased risk for developing different neurodegenerative diseases. To date UA metabolism has not been studied in FRDA.

Method: We enrolled 56 FRDA (29 M/27 F) and 30 (16M/14F) healthy controls (HC) without history of cancer, haemolytic or pernicious anaemia, alcoholism, gout, heart, kidney, liver, and endocrine disease, uncontrolled hypertension, or being treated with diuretics. Disease severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA). Extensive evaluation of blood biochemical metabolites including UA was performed in all subjects at baseline and 12 months later.

Results: Mean age ± SD for FRDA patients was 35.8±14.2 years and 40.8±13.5 for HC, the mean age at onset was 19.3±9.7, and disease duration was 16.0± 9.0. Serum UA levels resulted significantly lower in FRDA subjects (4.0±1.7) than in HC (4.9±1.2; CI 95% -1.44, -0.31; p=0.010), more among women than men in both groups. There was not a significant difference between UA level at baseline and after 12 months (+0.25; p=0.175).
We found a correlation between UA levels and BMI (p<0.001), blood glucose (p=0.006), haemoglobin (p=0.001), disease duration (p=0.001), AST (p=0.002) and transferrin (p=0.002), but neither with disease severity and duration, nor GAA expansion. At the multivariate linear regression, independent predictors of UA changes were neutrophils (p=0.002), baseline UA (p<0.001), and serum lipids (p=0.004).

Conclusion: Our results suggest that decreased AU levels might be associated with neurodegeneration in FDRA. The lack of a correlation with disease severity and duration, and GAA expansion suggests that AU levels might be already decreased in the early stage of disease, even if we do not exclude a possible correlation on higher numbers of patients and HC.

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