Myelin folates

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

Secondary folate deficiency resulting in megaloblastic anaemia and neuropathy (similar to folate deficiency). This is due to the impaired 1-carbon transfer needed for DNA/RNA synthesis and the impaired methyl transfer needed for synthesis of phosphatidylcholine used in myelin formation. 

Folate, a water-soluble B vitamin, is important in one-carbon metabolism. It plays a key role in amino acid metabolism and is important for the synthesis of DNA, some neurotransmittors and myelin, which is essential for the function of neurons. In utero, there is active transport of folate from mother to baby and, therefore, deficiency is seldom observed in newborns. 

Steinfeld, R., Grapp, M., Kraetzner, R., Dreha-Kulaczewski, S., Helms, G., Dechert, P., Wevers, R., Grosso, S., and Gartner J., 2009. FDolate receptor alpha defect causes cerebral folate transport deficiency a treatable neuro-degenerative disorder associated with disturbed myelin metabolism. American Journal of Human Genetics. 85 354-363. 

Vitamin B12 and folate are involved in the synthesis of methionine from homocysteine in the presence of methionine synthase for which 5-methyl tetrahydrofolate (THF) and methyl-vitamin B12 are cofactors. Methionine in turn along with adenosine triphosphate (ATP) forms 5 -adenosyl methionine (SAM), which is the only methyl group donor in the human central nervous system (CNS). SAM donates methyl groups in number of methylation reactions, involving synthesis of myelin, phospholipids, proteins and neurotransmitters (catecholamine and indoleamines). The methylation cycle is also of importance for the generation of active folate forms. When the methyl group is transferred, SAM is converted to S -adenosyl homocysteine (SAH) which is subsequently converted to homocysteine and adenosine. Hence, homocysteine, vitamin B12 and folate are linked together in one carbon cycle (Moretti et al. 2008). 

Clinical implications of methionine synthase inhibition The inhibition of methionine synthase due to vitamin B12 deficiency induces megaloblastic anemia that is clinically indistinguishable from that caused by folate deficiency. The hematological effect in both cases results in levels of 5,10-methyleneTHF that are inadequate to sustain thymidylate biosynthesis. Clinically, it is essential to ascertain whether the anemia is the result of folate deficiency or vitamin Bi2 deficiency by differential diagnostic techniques. Vitamin B12 is essential for the synthesis of myelin in nerve tissue, a function probably related to... 

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