Studies on MethylmalonicAcid in Humans.II. Relationshipbetween Concentrationsin Serum and Urinary Excretion,and the Correlation between Serum Cobalaminand Accumulationof MethylmalonicAcid

Methylmalonic acid (MMA) concentrations are increased in cobalamin(vitaminB12)deficiency, but the relative diagnos- tic usefulnessof determinationof MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutivepatientsadmittedfor clinicaland hema- tological evaluation because of low cobalamin concentra- tions in serum. Increasedconcentrationsof MMA in serum were found in 12 patients,in all of whoma clinicaldiagnosis of cobalamindeficiencywas established.By contrast,cobal- amindeficiencywas excludedinsevenof theeightremaining patients,who all had normalMMA concentrations.Here we report that linear relationshipsexist between MMA concen- trationsin serum(investigatedrange:0.05-34.2 1imol/L)and MMA concentrationsin urine (r = 0.74), concentrations relativeto creatinine(r = 0.98), and MMA excretion rates (r = 0.97) (P <0.001 in each instance).Our data are consistent withglomerularfiltrationand passivereabsorptionof MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinicalcobalamindeficiency(r = -0.69; P <0.01; n = 12); when the values for MMA were log transformed, the correlationwith cobalamin was much better (r = -0.84; P <0.0005).