High MMA most often reflects functional vitamin B12 deficiency — the main and usually correctable cause, as MMA accumulates when B12-dependent metabolism of methylmalonyl-CoA stalls. It is more specific to tissue B12 status than serum B12.
Non-B12 causes: reduced kidney function (the most important confounder, from decreased clearance), dehydration, hypothyroidism, pregnancy, and gut bacterial overgrowth (SIBO). Markedly high levels in infants or children suggest inherited methylmalonic acidemia.
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