Venditti, Charles (NHGRI)
Manoli, Eirini (Irini) (NHGRI)
Occupational Safety and Health
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 invented a series of assays to assess hepatic MUT activity using a stable isotopic tracing assays to measure MUT function to assess corrective therapy on hepatic mitochondrial function. The assays involve preparation of the isotope, mixing the isotope, dosing the isotope, collecting breaths from the patient, measuring the enrichment of the isotope in expired CO2, and then calculating the dose recovered/percent oxidized. These assays could be applied to propionate oxidation disorders, including all forms of propionic acidemia, methylmalonic acidemia, cobalamin defects ( cblA-J), vitamin B12 and biotin deficiency; disorders that affect hepatic mitochondrial metabolism; for testing the effects of drugs that affect hepatic metabolism.
Monitor mitochondrial dysfunction responses to therapeutics before showing clinical symptoms of the late stage kidney failure.
This is the only non-invasive, VCO2, label dosing, breath collection, measurement of 1-C-13 enrichment and calculations