How are serum folic acid, methylmalonic acid, and homocysteine values used to differentiate folic acid deficiency from pernicious anemia?

Updated: Feb 18, 2019
  • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

A serum folic acid assay is useful for ruling out folic acid deficiency. The reference range is 2.5-20 ng/mL. Blood should be drawn before patients have a single hospital meal since food can restore serum folic acid levels to normal. Red blood cell folic acid level is not influenced by food. (For more information, see Megaloblastic Anemia and Folic Acid Deficiency).  

A significantly decreased serum cobalamin level along with a typical clinical presentation, a characteristic peripheral smear, and an increased indirect bilirubin and LDH level is sufficient evidence for the diagnosis of a megaloblastic anemia.

Serum methylmalonic acid and homocysteine tests are important confirmatory tests but are not first-line tests. Elevated serum methylmalonic acid and homocysteine levels are found in patients with pernicious anemia. They probably are the most reliable test for cobalamin deficiency in patients who do not have a congenital metabolism disorder (see the table below). In the absence of an inborn error of methylmalonic acid metabolism, methylmalonic aciduria is a sign of cobalamin deficiency.

Table 1. Serum Methylmalonic Acid and Homocysteine Values Used in Differentiating Between Cobalamin and Folic Acid Deficiency (Open Table in a new window)

Patient Condition

Methylmalonic Acid

Homocysteine

Healthy

Normal

Normal

Vitamin B12 deficiency

Elevated

Elevated

Folate deficiency

Normal

Elevated


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