Diagnosis of vitamin B12 deficiency can be difficult, especially in the elderly. Methylmalonic acid (MMA) concentrations may be affected by renal dysfunction. Valente et al recommended the use of holotranscobalamin (holoTC) as a screening test for detection of vitamin B12 deficiency.


Holotranscobalamin consists of cobalamin bound to the transport protein transcobalamin. This fraction has receptor-mediated cellular uptake of the vitamin.

Serum HoloTC


> 30 pmol/L

no vitamin B12 deficiency

20 to 30 pmol/L


< 20 pmol/L

vitamin B12 deficiency


For indeterminate concentrations, erythrocyte folate levels should be performed. MMA may be helpful if renal function is known to be normal.


The ultimate criteria for vitamin B12 defiicency was a red blood cell cobalamin concentration < 33 pmol/L.


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