Assessment of vitamin B12 status

 Assessment of vitamin B12 status

Measurement of plasma concentrations of vitamin B12 is the method of choice, and several simple and reliable radioligand binding assays have been developed. A serum concentration of vitamin B12 below 110 pmol/l is associated with megaloblastic bone marrow, incipient anemia, and myelin damage. Below 150 pmol/l there are early bone marrow changes, abnormalities of the deoxyuridine monophosphate (dUMP) suppression test  and methylmalonic aciduria after a valine load.


The Schilling test for vitamin B12 absorption

The absorption of vitamin B12 can be determined by the Schilling test. An oral dose of [57Co] or [58Co]-vitamin B12 is given with a parenteral flushing dose of 1 mg of non-radioactive vitamin to saturate body reserves, and the urinary excretion of radioactivity is followed as an index of absorption of the oral mate-rial. Normal subjects excrete 16–45% of the radioac-tivity over 24 h, whereas patients lacking the intrinsic factor excrete less than 5%.

The test can be repeated, giving the intrinsic factor orally together with the radioactive vitamin B12; if the impaired absorption was due to a simple lack of intrinsic factor, and not to anti-intrinsic factor anti-bodies in the saliva or gastric juice, then a normal amount of the radioactive material should be absorbed and excreted.


Methylmalonic aciduria

 

Methylmalonyl-CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl-CoA arising in the catabolism of isoleu-cine, cholesterol, and (rare) fatty acids with an odd number of carbon atoms. Normally, it undergoes vitamin B12-dependent rearrangement to succinyl-CoA, catalyzed by methylmalonyl-CoA mutase. Vitamin B12 deficiency leads to an accumulation of methylmalonyl-CoA, which is hydrolyzed to methyl-malonic acid, which is excreted in the urine. Urinary excretion of methylmalonic acid, especially after a loading dose of valine, provides a means of assessing vitamin B12 nutritional status.

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