Low total antioxidant status is implicated with high 8-hydroxy-2-deoxyguanosine serum concentrations in phenylketonuria

Background: Phenylketonuria (PKU), an inborn error of metabolism, is treated with a low phenylalanine (Phe) lifelong diet, which can be characterized as vegetarian. 8-Hydroxy-2-deoxyguanosine (8-OHdG) is highly implicated in degenerative diseases. Objective: To evaluate the effect of plasma total antioxidant status (TAS) and Phe on the serum marker of DNA damage, 8-OHdG, in PKU. Methods: Twenty-four PKU patients on a strict diet (group A), 25 PKU patients on a “loose diet” (group B), and 24 healthy children (controls) participated in this study. Plasma TAS was evaluated spectrophotometrically. 8-OHdG and Phe were measured in blood with immunoassays. Results: TAS levels were significantly higher (P< 0.001) in group A (1458 ± 140 μmol/L) and controls (1452 ± 235 μmol/L) than those in group B (907 ± 150 μmol/L). In contrast, 8-OHdG serum levels were 2-fold higher in group B (0.22 ± 0.03 ng/mL) as compared with those in group A (0.11 ± 0.02 ng/mL) and 3-fold higher than those in controls (0.08 ± 0.02 ng/mL) (P< 0.001). As expected, Phe levels were also significantly higher in group B than those in the other study groups. Positive correlation coefficients were found between Phe and 8-OHdG levels, whereas negative correlations were evaluated between TAS and 8-OHdG in all groups. Conclusions: The high Phe and the low TAS plasma levels in PKU patients on a “loose diet” may induce DNA oxidation, as evidenced by the measured high 8-OHdG level in their sera. 8-OHdG evaluation may be a useful marker of increased risk for a neurodegenerative process.