Serum methylmalonic acid before and after oral L-isoleucine loading in cobalamin-deficient patients

Over a 1 1/2-year period, we measured concentrations of methylmalonic acid in serum before and after a standardized loading with oral L-isoleucine (100 mmol) in 13 patients admitted for evaluation of cobalamin deficiency. All patients had serum cobalamin values below 100 pmol l-1, but only 12 of the 13 patients were clinically confirmed cobalamin deficient. The clinically non-cobalamin-deficient patient had folate deficiency and was excluded. The serum methylmalonic acid concentrations before loading with isoleucine were above the upper reference limit (0.37 mumol l-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 mumol l-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 mumol l-1. The results show that a significant increase of an initially elevated serum methylmalonic acid concentration after isoleucine loading is a general finding in tissue cobalamin deficiency which strongly supports the diagnosis.