[Laboratory diagnosis of cobalamin deficiency. A comparative study of 2 serum cobalamin methods and serum...

The diagnosis of cobalamin deficiency is established traditionally by demonstration of lowered serum cobalamin, but, for many reasons it cannot be anticipated that the concentrations of cobalamins in the serum reflect the relationship between blood cobalamin and tissue cobalamin accurately. The blood methylmalonic acid which cannot be metabolized in cases of cellular cobalamin deficiency should, on the other hand, indicate the cobalamin available for the tissues. A blind, prospective, controlled investigation was undertaken to compare the clinical employability of a recently developed method for measurement of the concentration of methylmalonic acid in the serum with older and more recent methods of measuring serum cobalamins. The three methods classified 94, 72 and 74% of the patients correctly, respectively (n = 50). The results reveal that serum methylmalonic acid is a more sensitive and specific analysis for demonstrating whether cobalamin deficiency was present or not. Serum cobalamins measured by both methods are relatively insensitive and unspecific markers for cobalamin deficiency in the tissue. Low cobalamin concentrations do not indicate that the patient in question has cobalamin deficiency, and values in the lower half of the reference interval do not exclude cobalamin deficiency. Measurement of methylmalonic acid in the serum is recommended in patients with low-normal or low serum cobalamin.