Biochemical markers of B12 deficiency

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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

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