Propionic acidemia (PAemia) and
methylmalonic acidemia (MMAemia) are inborn errors of
propionate metabolism characterized by the accumulation of, respectively, propionic and l-methylmalonic
acids (and their metabolites) in the blood and tissues of affected patients. The conditions lead to severe metabolic complications in the neonatal period and to long-term
neurological manifestations. Treatment for these disorders consists of a
protein-restricted diet, supplemented with synthetic formulas of
amino acids, but excluding
isoleucine,
threonine,
valine and
methionine; and
l-carnitine, to promote detoxication. In vitro and in vivo studies have demonstrated that
lipid and
protein oxidative damage may be involved in the pathophysiology of these diseases, but DNA damage has not been fully investigated. In this work, we evaluated in vitro the effects of PA and MMA, in the presence or absence of
l-carnitine, on DNA damage in peripheral leukocytes, as determined by the alkaline comet assay, using
silver staining and visual scoring. PA and MMA induced
a DNA damage index (DI) significantly higher than that of the control group.
l-Carnitine significantly reduced PA- and MMA-induced DNA damage, in a concentration-dependent manner. Our findings indicate that PA and MMA induce DNA damage and
l-carnitine is able to prevent this damage.