BOF: General (Red Cell)

Regarding folic acid requirements, which of the following statements is true?

a) Elevated serum methylmalonate and homocysteine level are sensitive indicators of folic acid deficiency

b) Dialysis patients should take daily folic acid supplementation

c) Folic acid replacement should be initiated prior to the initiation of cobalamin replacement therapy

d) Patients with chronic haemolytic disorders should take folic acid replacement at times of worsening haemolysis

e) Serum folate gives a good reflection of folate stores

Answer:

b) Dialysis patients should take daily folic acid supplementation

Explanation:

Serum folate levels reflect recent folate intake, whereas red cell folate is a better measurement of tissue folate stores. Red cell folate may also be reduced in cobalamin (Vitamin B12) deficiency and this must be borne in mind when interpreting results. If folic acid alone is replaced in a cobalamin deficient patient, neurological symptoms may be precipitated, in particular subacute combined degeneration of the cord. If both folate and cobalamin stores are low, cobalamin replacement should be initiated first.

Serum homocysteine level is elevated in folic acid deficiency as well as in cobalamin deficiency since both factors are required for the conversion of methylTHF to THF by trans-methylation of homocysteine (forming methionine). However, cobalamin but NOT folate is required for the conversion of methylmalonyl CoA to succinyl CoA and therefore methylmalonate levels remain unchanged in folate deficiency, and are elevated in B12 deficiency.

Patients with chronic haemolysis have increased demand for folic acid and should therefore receive daily folate supplementation regardless of the degree of their haemolysis. Dialysis patients become folate deficient secondary to loss through the dialysis membrane and therefore also require daily supplementation.

Reference:

Devalia, V., Hamilton, M. S., Molloy, A. M. and the British Committee for Standards in Haematology (2014), Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology, 166: 496–513. doi: 10.1111/bjh.12959