MMUT (methylmalonyl-CoA mutase) catalyzes the reversible isomerization of methylmalonyl-CoA to succinyl-CoA, a key tricarboxylic acid cycle intermediate. 1 The enzyme localizes to the mitochondrial matrix and requires cobalamin (vitamin B12) as a cofactor. 1 MMUT processes metabolic intermediates from branched-chain amino acid degradation and odd-chain fatty acid metabolism. Deficiency of MMUT causes methylmalonic acidemia (MMA), the most common inherited organic acid metabolic disorder in China. 2 The disease presents with variable severity depending on MMUT mutations; for example, the c.1663G>A variant associates with milder phenotypes and better vitamin B12 responsiveness compared to other mutations. 3 4 Approximately 30-37% of completely B12-responsive patients remain healthy, while nonresponsive patients face 60% neurocognitive impairment rates. 4 Pathologically, MMUT deficiency induces mitochondrial dysfunction through impaired PINK1/Parkin-mediated mitophagy, allowing dysfunctional mitochondria accumulation and epithelial stress. 5 MMUT-deficient cells show compensatory metabolic shifts, including increased glutamine-dependent anaplerosis and secondary propionyl-CoA oxidation pathways. 6 Early diagnosis through newborn screening with vitamin B12 administration significantly improves outcomes, with screened patients showing 50.6% healthy outcomes versus 15.3% in unscreened cohorts. 2