[mrsD]

That is a complex question. I haven't seen much on this
as a medical problem, or on PubMed.

It is always possible because of some genetic flaw, the chemistry can get messed up, when enzymes don't work.

We have an article on Health news headlines, on twins today, and DNA flaws, that occur with aging. It maintains that DNA strands break and fail to perform in some people with aging.

http://neurotalk.psychcentral.com/thread164384.html

The following are some complex examples of the chemistry:

http://chemwiki.ucdavis.edu/Biologic...in/Cobalamin_1

The "R" group varies among the different cobalamins:
http://chemwiki.ucdavis.edu/Biologic...ymes/Cobalamin

This is an example of a specific use of cobamamide:
http://en.wikipedia.org/wiki/Cobamamide

For most intensive purposes, people who do not respond to
methyl B12, may have some genetic need for another type.
That I think is highly specialized, and difficult to find at the layman level.

from Dr. Sahelian MD:
http://www.raysahelian.com/methylcobalamin.html

Four cobalamines (methyl-, hydroxy-, adenosyl- and cyancobalamines) are considered as natural forms of vitamin B12 in human and animal tissues. Methyl- and adenosylcobalamines are the coenzymes of more than 10 enzymes, catalyzing important reactions of lipid, carbohydrate and protein metabolism. The four natural forms of vitamin B12 are interconverted in presence of corresponding enzymatic systems. Content of individual forms of cobalamines and of corresponding coenzymes depends on the function of enzymatic systems involved in their synthesis as well as on the enzymes, which use these derivatives as coenzymes. Spectra of cobalamines in human and animal bodies are dynamic systems, distinctly and specifically responding to various effects.

Thus genetic failure can be serious...but I have no idea how that would be identified. I would think failure to respond, would suggest trying another form. But I don't think this is very common.