Vitamin B12 Deficiency

Cycling of vitamin B12 and maintenance of activity of vitamin B12 is dependent not only on the presence of sufficient vitamin B12, but also the presence of the co-factors FAD/FMN/NADPH and folate. The rate at which the "helper" or co-enzymes function is in turn dependent upon the structures of the enzymes, and hence upon the genetics of the enzymes. Variability in activity of enzymes such as methionine synthase (MTR), methionine synthase reductase (MTRR) and methylene tetrahydrofolate reductase, are therefore intimately connected with the function of vitamin B12. In addition the receptors involved in the uptake of transcobalamin -bound vitamin B12 (TCN) and the removal of modified transcobalamin (FUT), have also been shown to have a role in the maintenance and levels of vitamin B12. It is these genetics and their associations that are the subject of the appropriate tags on MTHFR, MTRR, MTR, FUT, and TCN.

Further to these proteins, there are also a series of mutations in the gene involved in the production of the Intestinal vitamin B12 binding protein, Gastric Intrinsic Factor (GIF), and mutations in GIF have been associated with Intrinsic Factor deficiency and subsequent malabsorption of vitamin B12 (cobalamin). Thus "The signs of Cbl malabsorption are general weakness, slow growth, developmental delays and learning difficulties, dementia, psychological problems, neurodegeneration of the spinal chord, increased rate of infections due to neutropenia, thrombocytopeneia and megaloblastic anemia with lethal consequences if not treated (Tanner etal, 2012).

Tanner etal, 2012 Inherited cobalamin malabsorption:.... https://www.ncbi.nlm.nih.gov/pubmed/22929189