Dr. Forman is a family physician at Providence Seward Medical Center in Seward, Alaska. He is a reviewer and Ms. Becker is an editor for DynaMed (www.dynamicmedical.com), a database of comprehensive updated summaries covering nearly 2,000 clinical topics.

Prevalence
• 13%-15% of elderly patients
• 31% of post-gastric surgery patients
• 41% of long-term-care residents
• 6%-30% of patients taking metformin (Glucophage)

Significance
• Can cause megaloblastic anemia and neurologic problems
• Significance of subclinical deficiency unclear

ICD-9 codes
• 266.2 vitamin B12 deficiency
• 281.0 pernicious anemia
• 281.1 other vitamin B12 deficiency anemia
• 336.2 subacute combined degeneration of spinal cord in diseases classified elsewhere

Physiology
• Absorption occurs in stomach, duodenum, and terminal ileum and requires intrinsic factor and R proteins.
• B12 stored in liver can meet needs for years in adequately nourished persons.
• Metabolic function of B12 is 1-carbon transfer for folate metabolism.

Etiology
• B12 in animal products (especially liver, kidney, milk, eggs, fish, and cheese), fortified foods, supplements
• Inadequate diet: rare and usually seen in vegans or strict
• B12 malabsorption is major cause
—Lack of gastric intrinsic factor (pernicious anemia)
—Lack of gastric acid
—Postgastrectomy
—Diseases of terminal ileum (ileal resection, inflammatory bowel disease, celiac disease, fish tapeworm)
—Pancreatic insufficiency
—Bacterial overgrowth; Helicobacter pylori infection
—Idiopathic malabsorption
—Uncommon causes may include long-acting hyperthyroidism, metformin (Glucophage), or high-dose folic-acid supplementation.

Complications
• Pernicious anemia
• Subacute combined degeneration of spinal cord
• Psychiatric disease

Clinical evaluation
• Anemia symptoms: weakness, fatigue, light-headedness, pallor, tachycardia, dyspnea, congestive heart failure
• GI symptoms: anorexia, intermittent diarrhea, constipation
• Past history: Crohn's disease, gastric or ileal surgery
• Neurologic evaluation
—Symptoms may include paresthesias, ataxia, loss of position and vibration senses, memory impairment, depression, dementia, distal weakness.
—Neurologic findings associated with subacute combined degeneration of spinal cord
 

  • Dissociated sensory loss (vibration sense in legs and trunk)
  • Motor defects in legs
  • Severe truncal and leg ataxia
  • High-steppage gait

    • Testing
    • Serum B12 not sensitive or specific for tissue deficiency
    • Elevated methylmalonic acid (MMA) or homocysteine levels may confirm B12 deficiency.
    • Complete blood count may reveal megaloblastic anemia, possible thrombocytopenia, and neutropenia (late finding).
    • Folate (to rule out folate deficiency)
    • Rule out other causes of anemia with reticulocyte count, peripheral blood smear, thyroid function tests, liver function tests.
    • Anti-intrinsic factor antibody and serum gastrin level for diagnosis of pernicious anemia
    • Schilling test useful if other studies inadequate: up to four phases, each with 24-hour urine collection to measure excretion of oral radioactive B12
    —Phase I: Normal excretion means dietary deficiency.
    —Phase II: Add intrinsic factor, normal excretion means pernicious anemia.
    —Phase III: Add antibiotics, normal excretion means bacterial overgrowth.
    —Phase IV: Add pancreatic extract, normal excretion means pancreatic insufficiency.
    —Persistent low excretion may indicate renal failure or inadequate urine collection.

    Prognosis
    • Requires lifelong B12 supplementation
    • Most symptoms reversible if treated early
    • Dementia resulting from B12 deficiency may not be reversible.

    Treatment
    • B12 clearly beneficial for megaloblastic anemia or neurologic disease due to B12 deficiency
    • Benefit of supplementation in subclinical B12 deficiency unclear
    • Synthetic B12 (cyanocobalamin) 1,000 µg IM monthly
    • Oral vitamin B12 replacement (500-1,000 µg/day) may be as effective as IM replacement.
    • Vitamin B12 500 µg nasal spray each week approved for maintenance treatment of B12 deficiency once hematologic parameters normalized

    Follow-up
    • Mean corpuscular volume should return to normal in six weeks.
    • Neurologic correction takes about 18 months.

    Prevention
    • Adequate B12 intake from foods or supplements
    —Recommended Dietary Allowance for adults 2.4 µg/day
    —Fortified foods or supplements recommended for persons >50 years old
    • Prophylactic B12 supplementation may prevent deficiency in high-risk populations (elderly, vegans, postgastrectomy patients). • Consider screening or B12 supplementation for patients on prolonged H2 blocker or proton pump inhibitor treatment.

    See (www.dynamicmedical.com), for references.