Vitamin B12 Deficiency

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Contents 1 Etiology 2 Epidemiology 3 Pathology 4 Clinical-manifestations 5 Laboratory 6 Diagnostic-procedures 7 Radiology 8 Complications 9 Differential-diagnosis 10 Management 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Etiology

• pernicious anemia ( autoimmune) {most common cause [5]}
• food- cobalamin malabsorption

• inability to split cobalamin from its binding in food {50% of cases} [6]

• dietary: vegans
• hypochlorhydria, atrophic gastritis
• post surgical: gastrectomy or ileal resection
• pancreatic insufficiency [20]
• Crohn's disease
• bacterial or parasitic overgrowth of small intestine

• blind loop syndrome
• Diphyllobothrium latum, Giardia lamblia, Taenia [15]

• inherited condition in which a histologically normal stomach secretes either an abnormal intrinsic factor or none at all
• pharmaceutical agents may contribute

• chronic use of nitrous oxide oxidizes cobalamin
• drugs which interfere with absorption of vit B12

• neomycin
• colchicine
• ethanol
• metformin (esp without Ca+2 supplementation) [13,18]

• chronic proton pump inhibitor use

• Helicobacter pylori infection

Epidemiology

• 3-5% of elderly [3]

Pathology

• subacute combined degeneration of peripheral nerves & spinal cord

• changes begin in the posterior columns &/or lateral columns of the lower cervical & upper thoracic spinal cord
• demyelination & wallerian axonal degeneration
• phagocytosis by macrophages & reactive astrocytosis
• increased tissue levels of methylmalonyl CoA & its precursor propionyl CoA lead to synthesis of non- physiologic fatty acids & their incorporation into neuronal lipids [7]

• cerebral hemisphere pathology less well defined
• pernicious anemia
• megaloblastic anemia

Clinical-manifestations

• paresthesias early in the course of the illness
• signs & symptoms of anemia
• abnormal sensation of position & vibration ( posterior column)
• weakness
• spasticity
• gait disturbance
• diminished deep tendon reflexes
• decreased pain & temperature sensation
• psychiatric disturbances

• mood & personality changes
• psychosis
• delirium
• memory impairment ( dementia, Wernicke's syndrome [10])

• jaundice may result from ineffective erythropoiesis
• 'beefy red' glossitis
• orthostatic tremor (may be presenting symptom)
• seizures (unusual) [11]

Laboratory

• features of megaloblastic anemia may be observed

• complete blood count ( CBC)

• anemia may or may not be present
• MCV may be elevated or normal

• peripheral blood smear may show macrocytes & hypersegmented neutrophils

• serum vitamin B12 level

• < 200 pg/mL suggestive of vitamin B12 deficiency
• < 100 pg/mL is diagnostic
• serum levels may be normal with defective conversion of cobalamin to active coenzyme

• Schilling test ( gold standard)
• increased urinary methylmalonic acid
• serum methylmalonic acid is increased
• serum homocysteine may be elevated [12]
• evidence of pernicious anemia

• serum gastrin levels is often high
• intrinsic factor antibody is often positive
• gastric pH may be high with pernicious anemia

• deoxyuridine suppression test ( dUST) {rarely done}
• vitamin B12 binding capacity
• serum holotranscobalamin 2 is diminished [16]

• may not be useful in patients with renal insufficiency

Diagnostic-procedures

• electroencephalography is abnormal (50%) [6]
• evoked potentials are abnormal (50%) [6]

Radiology

• magnetic resonance imaging of the cervical/ thoracic spine

• hyperintensity of the posterior columns &/or lateral columns on T2-weighted images [8]
• MRI abnormalities may persist after treatment [8]
• pathology generally involves both posterior columns & lateral columns or cord in general at thoracic level

Complications

• poor response to pneumovax in elderly patients with vitamin B12 deficiency
• increased risk of gastric cancer & gastric carcinoid
• also see pernicious anemia
  
• disease interaction(s) of vitamin B12 deficiency with urinary incontinence

Differential-diagnosis

• copper deficiency (overlap of clinical manifestations) [20]

Management

• intrinsic factor deficiency & failure of ileal absorption

• 1 mg IM weekly for 1 month
• 1 mg IM monthly for life
• 1000-2000 ug PO QD ( sublingual) [19]

• simple vitamin B12 deficiency:

• oral vitamin B12 ( cyanocobalamin) 25-250 ug QD ( RDA is 2 ug/day)
• adverse effects:

• itching
• diarrhea

• food-cobalmin malabsorption:

• 1000-2000 ug PO QD [3,17]
• treatment of choice for all vitamin B12 deficiency [3,19]

• folate supplementation can improve (or mask) the anemia of vitamin B12 deficiency, but will not prevent or improve the neuropathology
• consider endoscopy:

• increased risk of gastric cancer & gastric carcinoid

• prognosis

• behavioral symptoms & peripheral neuropathy respond within 6 months of treatment, but often fail to completely remit
• it is rare for the dementia to reverse
• hematologic values normalize in 2 months
• no evidence that finding a cause for B12 deficiency improves outcomes [20]; treat emipirically with cyanocobalamin 1 mg sublingual QD

More General Terms

• gastrointestinal disease
• hypovitaminosis (vitamin deficiency)

Additional Terms

• intrinsic factor (IF)
• megaloblastic anemia
• methylmalonate in serum
• pernicious anemia
• Schilling test
• subacute combined degeneration of spinal cord
• vitamin B12 in serum/plasma
• vitamin B12; cobalamin

Internet Database

OMIM: 250940

References

1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 577-78, 1017
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 411
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
4. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
5. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 655-56
6. Carmel R Ann Rev Med 51:357, 2000 PMID: [1]
7. Harrison's Online, Chapter 107, McGraw Hill, 2002
8. Yu MK & Rodgers GM, Am J Hematol 65:83, 2000 PMID: [2]
9. Bassi SS et al Neuroradiology 41:210, 1999 PMID: [3]
10. Greenfield's Neuropathology, 5th ed, Adams JH & Duchen LW (eds), Oxford University Press, New York, 1992, pg 832
11. Kumar S Nuerol India 52:122, 2004 PMID: [4]
12. Kaptan K & Beyan C Vitamin B12 deficiency as a cause of hyperhomocysteinaemia. Aliment Pharmacol Ther. 19(6):703, 2004 PMID: [5]
13. Buvat DR. Use of metformin is a cause of vitamin B12 deficiency. Am Fam Physician. 69(2):264, 2004 PMID: [6]
14. Wald NJ et al, Vitamin B-12 and folate deficiency in elderly persons. Am J Clin Nutr. 79(2):338 2004 PMID: [7]
15. Vuylsteke P et al, Case of megaloblastic anemia caused by intestinal taeniasis. Ann Hematol. 2004 Jan 17 PMID: [8]
16. Hvas AM & Nexo E. Holotranscobalamin as a predictor of vitamin B12 status. Clin Chem Lab Med. 41(11):1489-92. 2003 PMID: [9]
    - Herrmann W et al, Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. 41(11):1478-88. 2003 PMID: [10]
17. Prescriber's Letter 12(7): 2005 Oral Vitamin B12 in the Treatment of Vitamin B12 Deficiency Detail-Document#: [11] (subscription needed) [12]
18. Prescriber's Letter 16(8): 2009 Metformin-Induced Vitamin B12 Deficiency: Can it Lead to Peripheral Neuropathy? Detail-Document#: [13] (subscription needed) [14]
19. Prescriber's Letter 18(8): 2011 Treatment of Vitamin B12 Deficiency Detail-Document#: [15] (subscription needed) [16]
20. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010

vitamin B12 deficiency