Diagnostic Considerations

In a patient with combined folate and vitamin B-12 deficiency, if only the folate deficiency is recognized, folic acid supplementation may be sufficient to drive the production of active 5 methyl tetrahydrofolate (THF) in the absence of vitamin B-12. This results in improvement of the anemia but does not result in improvement of the function of other pathways dependent on B-12.

Clinically, this is apparent as a resolution of megaloblastic anemia, but with progressive dementia and long-tract neurologic deficits. This situation can be avoided by measuring levels of both vitamins, then evaluating and treating both deficiencies, if found.

Other conditions to consider include the following:

Aplastic anemia
Celiac disease
Ecchymoses
Granulocytopenia
Hyposplenism
Myeloproliferative disorders
Neutropenia
Pancytopenia
Tapeworm infection (cestodiasis)
Imerslund-Grasbeck disease
Thiamine-responsive megaloblastic anemia^{[2, 3]}

Go to Pediatric Chronic Anemia, Anemia of Prematurity, Donath-Landsteiner Hemolytic Anemia, Pediatric Acute Anemia, and Fanconi Anemia for complete information on these topics.

Differential Diagnoses

Workup

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Olsen BS, Hahnemann JM, Schwartz M, Østergaard E. Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood. Pediatr Diabetes. 2007 Aug. 8(4):239-41. [QxMD MEDLINE Link].
Wolffenbuttel BHR, Wouters HJCM, Heiner-Fokkema MR, van der Klauw MM. The Many Faces of Cobalamin (Vitamin B₁₂) Deficiency. Mayo Clin Proc Innov Qual Outcomes. 2019 Jun. 3 (2):200-14. [QxMD MEDLINE Link]. [Full Text].
Baumgartner MR. Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E. Handb Clin Neurol. 2013. 113:1799-810. [QxMD MEDLINE Link].
Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol. 2006 Jul. 134(2):125-36. [QxMD MEDLINE Link].
Duma A, Cartmill C, Blood J, Sharma A, Kharasch ED, Nagele P. The hematological effects of nitrous oxide anesthesia in pediatric patients. Anesth Analg. 2015 Jun. 120 (6):1325-30. [QxMD MEDLINE Link].
Stredny CM, Frosch O, Singhi S, et al. Vitamin B12 Deficiency Presenting with Neurological Dysfunction in an Adolescent. Pediatr Neurol. 2016 Sep. 62:66-70. [QxMD MEDLINE Link].
Korenke GC, Hunneman DH, Eber S, Hanefeld F. Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature. Eur J Pediatr. 2004 Apr. 163(4-5):196-201. [QxMD MEDLINE Link].
Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008 Jun. 29(2 Suppl):S101-11; discussion S112-5. [QxMD MEDLINE Link].
Erkurt MA, Aydogdu I, Dikilitas M, Kuku I, Kaya E, Bayraktar N, et al. Effects of cyanocobalamin on immunity in patients with pernicious anemia. Med Princ Pract. 2008. 17(2):131-5. [QxMD MEDLINE Link].
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Habeb AM, Flanagan SE, Zulali MA, et al. Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome. Diabetologia. 2018 May. 61 (5):1027-36. [QxMD MEDLINE Link]. [Full Text].
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Ozkale M, Sipahi T. Hematologic and Bone Marrow Changes in Children with Protein-Energy Malnutrition. Pediatr Hematol Oncol. 2013 Aug 29. [QxMD MEDLINE Link].
Dugué B, Ismail E, Sequeira F, Thakkar J, Gräsbeck R. Urinary excretion of intrinsic factor and the receptor for its cobalamin complex in Gräsbeck-Imerslund patients: the disease may have subsets. J Pediatr Gastroenterol Nutr. 1999 Aug. 29(2):227-30. [QxMD MEDLINE Link].
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Media Gallery

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. Photo courtesy of Marcel E Conrad, MD.

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Author

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.