Folic Acid Deficiency Workup

  • Author: Angela Gentili, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Dec 1, 2011
 

Laboratory Studies

  • Serum folate (reference range 2.5-20 ng/mL) and serum cobalamin (reference range 200-900 pg/mL)
    • 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.
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Procedures

Bone marrow biopsy and aspirate may show a hypercellular bone marrow with a megaloblastic maturation of cells (see Images 4-6 or below). This cannot be differentiated from changes observed with vitamin B-12 deficiency.

Histologically, the megaloblastosis caused by foliHistologically, the megaloblastosis caused by folic acid deficiency cannot be differentiated from that observed with vitamin B-12 deficiency. Peripheral smear of blood in a patient with pernicPeripheral smear of blood in a patient with pernicious anemia. Macrocytes are observed and some of the red blood cells show ovalocytosis. A 6-lobed polymorphonuclear leucocyte is present. Bone marrow aspirate from a patient with untreatedBone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above.
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Contributor Information and Disclosures
Author

Angela Gentili, MD  Director of Geriatrics Fellowship Program, Associate Professor, Department of Internal Medicine, Virginia Commonwealth University Health System and McGuire Veterans Affairs Medical Center

Angela Gentili, MD is a member of the following medical societies: American Geriatrics Society

Disclosure: Nothing to disclose.

Coauthor(s)

Muhammad Vohra, MD  Assistant Professor, Department of Internal Medicine, Hamdard University Hospital, Pakistan

Muhammad Vohra, MD is a member of the following medical societies: American Geriatrics Society

Disclosure: Nothing to disclose.

Subir Vij, MD, MPH  Assistant Professor, Department of Medicine, Eastern Virginia Medical School; Medical Director, Portsmouth Community Health Center

Subir Vij, MD, MPH is a member of the following medical societies: American College of Physician Executives, American College of Physicians, and American Medical Association

Disclosure: Nothing to disclose.

David Kuan-Hua Chen, MD  Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center

David Kuan-Hua Chen, MD is a member of the following medical societies: Alpha Omega Alpha and Phi Beta Kappa

Disclosure: Nothing to disclose.

Waleed Siddiqi, MD  Fellow in Geriatrics, Department of Internal Medicine, Division of General Internal Medicine/Primary Care, Medical College of Virginia

Waleed Siddiqi, MD is a member of the following medical societies: American College of Physicians and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Pradyumna D Phatak, MBBS, MD  Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD, is a member of the following medical societies: American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Ahmed Mosalem, MD, to the development and writing of this article.

References

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The chemical structure of folic acid and amethopterin (methotrexate), a folic acid antagonist, shows the similarity of structure.
The transformation of formiminoglutamic acid to glutamic acid is dependent upon both vitamin B-12 and tetrahydrofolate. In contrast, the transformation of homocysteine to methionine is a vitamin B-12–dependent reaction.
Both folic acid and vitamin B-12 participate in the synthesis of DNA and RNA.
Histologically, the megaloblastosis caused by folic acid deficiency cannot be differentiated from that observed with vitamin B-12 deficiency.
Peripheral smear of blood in a patient with pernicious anemia. Macrocytes are observed and some of the red blood cells show ovalocytosis. A 6-lobed polymorphonuclear leucocyte is present.
Bone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above.
 
 
 
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