Red Blood Cell Metabolism In Patients With Propionic Acidemia

Propionic acidemia (PA) is a rare autosomal recessive disorder with an estimated incidence of 1:100,000 live births in the general population. Due in part to an insufficient understanding of the disease's pathophysiology, PA is often associated with complications, and in severe cases can cause coma and death. Despite its association with hematologic disorders, PA's effect on red blood cell metabolism has not been described. Mass spectrometry-based metabolomics analyses were performed on RBCs from healthy controls (n = 10) and PKD patients (n = 3). PA was associated with a significant decrease in the steady state level of glycolytic products and the apparent activation of the PPP. The PA samples showed decreases in succinate and increases in the downstream dicarboxylates of the TCA cycle. BCAAs were lowered in the PA samples and C3 carnitine, a direct metabolite of propionic acid, was increased. Trends in the markers of oxidative stress including hypoxanthine, allantoate and spermidine were the opposite of those associated with elevated ROS burden. The alteration of short chain fatty acids, the accumulation of some medium chain and long chain fatty acids, and decreased markers of lipid peroxidation in the PA samples contrasted with previous research. Despite limitations from a small cohort, this study provides the first investigation of RBC metabolism in PA, paving the way for targeted investigations of the critical pathways found to be dysregulated in the context of this disease.