Biochemical markers of B12 deficiency

Previous Post : Vitamin B12 levels

Serum Holo-Transcobalamin
  • Vitamin B12 bound to Transcobalamin = Holo-TC
  • Represents 10 -30% of total Vitamin B12 present in serum
  • Cells take up Holo-TC via receptor-mediated endocytosis by TC receptor.
  • Marker of bioactive Vitamin B12
  • Circulating levels of plasma holoTC may be an index of absorption of B 12 as well as availability of the vitamin to cell
  • Correlates well with Vitamin B12 concentration in RBCs
  • Normal range of holo-TC is 20 – 125 pmol/L
Serum Methyl Malonyl CoA(MMA) and Homocysteine(HCy)
  • Functional biomarkers
  • Sensitive indicators of tissue vitamin B12 deficiency
  • High in > 90% B12-deficient patients
  • Increase before B12-levels fall- sensitive biomarkers of a subclinical underlying state of B12 deficiency 

MMA vs Homocysteine

  • Sensitivityand specificity for Vitamin B12 deficiency: MMA> Homocysteine
    • Vitamin B12 deficiency: Both MMA and HCy raised
    • Folate deficiency: Only HCy raised
  • Homocysteine -Increased levels:
    • Folate deficiency (MMA is not elevated in Folate deficiency)
    • Pyridoxine deficiency
    • Hypothyroidism
  • MMA – Increased levels
    • Renal insufficiency (both MMA and Vitamin B12 increaseBlind loop syndrome –> intestinal microbes–>synthesize propionate, a precursor of MMA–>microbial-derived MMA in plasma. 
    • Isolated MMA elevation  does not mean Vitamin B12 deficiency

Limitations of  Holo-TC as a first line test:

  • Additional research needed to understand homeostasis
  • Insufficient sensitivity noted in elderly
  • Variations of Holo-TC levels in inborn errors of B12 metabolism is unknown
  • Low levels of Holo-TC without total B12 deficiency seen in chemotherapy, macrocytosis.
  • Costlier than total B12

Cost wise comparisons

  • Holo Transcobalamin  = 2 X Vitamin B12
  • Methylmalonic acid levels = 4 x Vitamin B12
  • Homocysteine levels = Vitamin B12 levels

NEXT POST – Vitamin B12 deficiency- Practice points 

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