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

Abstract

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 μmol l^-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 μmol l^-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 μmol 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.

Key Words:

• precursor loading
• tissue cobalamin deficiency
• vitamin B12 deficiency