What is the role of lab testing in the workup of folic acid deficiency?

Updated: Sep 14, 2018
  • Author: Katherine Coffey-Vega, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

As the initial test, ruling out cobalamin deficiency is very important because deficiency of folic acid and vitamin B-12 produce overlapping neurologic manifestations, and both cause megaloblastic anemia, but folate treatment will not improve neurologic abnormalities due to cobalamin deficiency. [43] The reference range for serum cobalamin is 200-900 pg/mL

The reference range of serum folate is 2.5-20 ng/mL. By statistical definition, 2%-5% of healthy individuals will have a serum folate level of less than 2.5 ng/mL; hence, the serum folate level cannot be used alone to establish the diagnosis of folate deficiency. Therefore, the serum folate test is definitive only when the level is greater than 5.0 ng/mL, which rules out folate deficiency. Otherwise, additional follow-up tests include serum homocysteine (reference range 5-16 mmol/L), which is elevated in vitamin B-12 and folate deficiency, and serum methylmalonic acid (reference range 70-270 mmol/L), which is elevated in vitamin B-12 deficiency only.

Red blood cell folate levels (reference range >140 ng/mL) tend to reflect long-term folate status rather than acute changes in folate that are reflected in serum folate levels, although many confounding factors, such as transfused red cells, can make this unreliable as a test for folate deficiency states.

Other than folate or cobalamin deficiency, the only other confounding causes for elevation of these compounds include renal failure, intravascular volume depletion, and some rare inborn errors of metabolism involving folate or cobalamin-dependent enzymes.


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