Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.

Abstract

Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of 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 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005).

Effects of 6 Weeks of Parenteral Cobalamin Supplementation on Clinical and Biochemical Variables in Cats with Gastrointestinal Disease

“…Although there are no data on renal clearance of circulating MMA in cats, it has been shown that urinary excretion of serum MMA relative to that of creatinine was <1 in human patients. 15,[31][32][33] It was proposed that an unknown percentage of serum MMA is not excreted by the kidney, but instead is metabolized via unknown pathways. [31][32][33] If this theory is valid and applicable to cats, individual differences in metabolism might have affected urinary excretion of MMA, which would explain the discrepancy in serum and urine MMA concentrations.…”

“…6,[12][13][14] In humans, a linear relationship exists between serum and urine MMA concentrations. 15 In veterinary medicine, comparisons between serum and urine MMA concentrations are lacking.…”

Plasma total-homocysteine in anorexia nervosa

“…Plasma tHcy, as well as methylmalonic acid in serum and urine (Rasmussen et al, 1989), have been demonstrated to be sensitive markers of intracellular folate and cobalamin de®ciency (Allen et al, 1990). tHcy was measured and found signi®cantly high in anorexia patients.…”

Advanced Age as a Risk Factor for Folate‐Associated Functional Cobalamin Deficiency

“…A retrospective review of the medical records of all ambulatory, community‐dwelling adults evaluated by the author in an internal medicine clinic at a university‐based staff model health maintenance organization for possible cobalamin deficiency between August 1, 1993, and June 30, 2005, in whom concurrent cobalamin, serum folate, and MMA levels were obtained was conducted as previously described . Because both renal insufficiency and diabetes mellitus increase MMA and homocysteine levels, individuals were excluded if renal function was impaired (serum creatinine levels >1.5 mg/dL in men, >1.3 mg/dL in women) or if diabetes mellitus was present . Ten individuals with cobalamin levels below the reference range (≤200 pg/mL) and six with cobalamin levels above the reference range (>1,100 pg/mL) were also excluded from analysis.…”