Folic Acid Deficiency Workup
- Author: Katherine Coffey-Vega, MD; Chief Editor: Emmanuel C Besa, MD more...
Serum folate (reference range 2.5-20 ng/mL) and serum cobalamin (reference range 200-900 pg/mL) testing
As the initial test, ruling out cobalamin deficiency is very important because folate treatment will not improve neurologic abnormalities due to cobalamin deficiency.
By statistical definition, 2-5% of healthy individuals will have serum folate 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 useful only to rule out folate deficiency in patients with serum folate greater than 5.0 ng/mL. Otherwise, additional follow-up tests include serum homocysteine (reference range 5-16 mmol/L), which is elevated in B-12 and folate deficiency, and serum methylmalonic acid (reference range 70-270 mmol/L), which is elevated in B-12 deficiency only.
Red blood cell folate levels (reference range >140 ng/mL) tend to reflect chronic 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.
Bone marrow biopsy and aspirate may show a hypercellular bone marrow with a megaloblastic maturation of cells (see the slides below). This cannot be differentiated from changes observed with vitamin B-12 deficiency.
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