Reference intervals for plasma vitamin B12 and plasma/serum methylmalonic acid in Danish children, adults and elderly

Abstract

Background: Plasma/serum vitamin B12 (B12) is often used to screen for B12 deficiency complemented with analysis of methylmalonic acid (MMA) in case of low B12. The concentration of both analytes likely depends on age, and we, therefore, aimed at establishing 95% age-adjusted reference intervals (RIs) for plasma B12 and serum/plasma MMA in the Danish population.

Methods: We collected and analysed blood samples from healthy children, adults, and elderly individuals and extracted routine clinical B12 and MMA results to establish RIs. We also evaluated the association between matching B12 and MMA results.

Results: We suggest the following RIs for plasma B12 and plasma/serum MMA, respectively. 0-<1 year: 180-1400 pmol/L, 0.10-1.25 µmol/L; 1-<11 years: 260-1200 pmol/L, 0.10-0.30 µmol/L; 12-<18 years: 200-800 pmol/L, 0.10-0.35 µmol/L; 18-<65 years: 200-600 pmol/L, 0.10-0.40 µmol/L; 65 + years: 200-600 pmol/L, 0.12-0.46 µmol/L. Finally, the proportion of patients with elevated MMA differed between age groups independently of B12 and was highest in children.

Conclusion: We propose new age-adjusted RIs for B12 and MMA and suggest that age-dependent cut-off values should be implemented if plasma B12 is used to screen for B12 deficiency.

Keywords: Methylmalonic acid; Reference intervals; Vitamin B12; Vitamin B12 deficiency.