Abstract
Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62–0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0–98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.
Highlights
Vitamin B12 (B12, or cobalamin) deficiency is a frequent condition that affects 1.5% of the general population [1,2], and up to 10–15% of subjects above 60 years old [3]
Among the 490 patients tested for B12 status, 144 (29.4%) had plasma B12 in the range 201–350 ng/L, of whom 127 patients had no missing data
Previous reports suggested that urinary methylmalonic acid (MMA) could become a good diagnostic marker of B12 deficiency due to its good stability in urine [19], its association with cellular B12 deficiency [45], and the absence of expected decrease of its urinary excretion before severe renal failure [24]
Summary
Vitamin B12 (B12, or cobalamin) deficiency is a frequent condition that affects 1.5% of the general population [1,2], and up to 10–15% of subjects above 60 years old [3]. The status of B12 deficiency was only based on the plasma B12 measurement, with a threshold around 200 ng/L (148 pmol/L) [4]. Plasma B12 does not correctly reflect the intracellular cobalamin status. Typical clinical and biological signs of B12 deficiency can be observed in patients with plasma B12 over ng/L, notably between and 350 ng/L [4,5,6,7]. The interval of plasma B12 between 201 and 350 ng/L defines a “grey zone” where the B12 status remains uncertain
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