Oxidative Stress and Inflammation in Methylmalonic and Propionic Acidemias: A Review.

Abstract

Methylmalonic acidemia and propionic acidemia are inherited organic acidemias resulting from deficiencies in the enzymes methylmalonyl-CoA mutase and propionyl-CoA carboxylase, respectively. Impaired activity of these enzymes leads to the accumulation of propionyl-CoA and methylmalonyl-CoA metabolites in tissues and biological fluids. The two disorders share similar clinical features, most notably severe neurological involvement. In the absence of early diagnosis and appropriate treatment, affected individuals may develop irreversible neurological injury, progress to coma, and, in severe cases, death. In this scenario, this review presents some findings from studies in patients, cells and animal models, evidencing that oxidative stress and inflammation plays a crucial role in the pathophysiology of methylmalonic acidemia and propionic acidemia. Furthermore, it allows us to understand the profile of oxidative stress and new perspectives for the treatment of these diseases. Decreased antioxidant defenses, as well as increased levels of markers of inflammation, oxidative damage to lipids, proteins and DNA were observed in animal models, cells and patients, possibly due to the increase in the production of reactive species caused by the accumulated metabolites. The literature also indicates that the use of specific antioxidants may provide benefits by improving the oxidative profile. Based on this evidence, it is widely accepted that oxidative stress and inflammation contribute to severe neurological damage in patients with methylmalonic acidemia and propionic acidemia.