Data Independent Acquisition Mass Spectrometry for Proteomic Advances into Isolated Methylmalonic Acidemia

摘要

This reaction is normally supported by adenosylcobalamin which is the MUT cofactor. The result of this enzymatic block is the accumulation of methylmalonyl-CoA that is hydrolyzed to form methylmalonic acid. As a biomarker of the disease, methylmalonic acid is identified and quantified in patients' body fluids, i.e., urine and blood by liquid chromatography - tandem mass spectrometry (LC-MS/ MS) or gas chromatography - mass spectrometry (GC-MS) to make a diagnosis. Other metabolites dosed for the diagnosis and the clinical monitoring of methylmalonic acidemia are propionylcarnitine, 3-OH-propionic acid, methylcitric acid, and the amino acids glycine and alanine. Since the first month of the newborn period, patients can show neurologic manifestations and metabolic instability with long-term complications, including severe neuronal impairment, developmental delay, kidney and liver disease, coma, and death. Also, acute metabolic decompensation and cardiac crises are frequent in these patients, so that early intervention is required.