Serum Protein Biomarkers that Predict the Response to Liver Directed Therapy in Methymalonic Acidemia (MMA) and Propionic Acidemia (PA)

Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. The most common cause of isolated MMA is genetic deficiency of the enzyme methylmalonyl-coA mutase (MUT), which, unfortunately for the affected patients, is also the most clinically severe. NHGRI scientist have discovered biomarkers previously described cytokines that has never been associated with MMA or propionic acidemia (PA) such as FGF-21 (fibroblast like-growth factor - 21). The cytokines have been studied in patients with mitochondrial myopathies and other unrelated metabolic disorders, but never MMA. These cytokines have also been associated with mitochondrial dysfunction but never studied in MMA or PA. These new biomarkers could be used to measure the effects of any intervention on hepatic MUT or PCC activity and the effects of hepatic MUT or propionyl-Co A carboxylase (PCC) deficiency, and the secondary mitochondropathy associated with MUT and PCC deficiency.