Abstract
Patients with the genetic defect, methylmalonic acidemia (MM-emia), have vomiting, ketoacidosis, failure to thrive and a high mortality. Clinically, patients are usually classified by their in vivo response to vitamin B12 i.e. some tend to normalize biochemically whereas others do not. Cell free extracts of liver and/or skin fibroblasts were assayed for mutase activity by measuring succinate formation from methylmalonylCoA. Vitamin B12 coenzyme (DBCC) synthesis was measured by incorporation of Co57 precursor into DBCC. 5 patients, clinically unresponsive, had no in vitro mutase activity and synthesized DBCC normally. 4 additional patients had normal in vitro mutase activity and defective DBCC formation. However, only 2 of the 4 were responsive in vivo. Intact fibroblasts were studied for conversion of propionate-1-14C to 14CO2. Good correlation of CO2 production was noted in the 5 lines with no mutase activity but variable results were found in the other 4.
Liver mutase activity accurately reflects fibroblast extract activity in any individual patient. Response by intact cells to B12 is variable in some patients. “Responsiveness” should be limited to the changes noted in vivo and should remain a clinical description rather than one to delineate possible mechanisms responsible for the defect.
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Morrow, G., Mahoney, M., Lebowitz, J. et al. METHYLMALONYLCoA CAKBONYLMUTASE (MUTASE) ACTIVITY IN VIVO AND IN VITRO-FURTHER EVIDENCE OF GENETIC HETEROGENEITY. Pediatr Res 8, 437 (1974). https://doi.org/10.1203/00006450-197404000-00580
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DOI: https://doi.org/10.1203/00006450-197404000-00580