Vitamin B12 deficiency

Dr Daniel J Bell et al.

Vitamin B12 deficiency, also known as hypovitaminosis B12 or hypocobalaminemia, is not uncommon, with potentially serious sequelae if not adequately treated.

Vitamin B12 deficiency presents with a wide spectrum of dysfunction, from no symptoms at all (i.e. subclinical disease) to florid CNS involvement and myelosuppression.

Many cases initially present with mild non-specific symptoms e.g. tiredness, usually a manifestation of the associated megaloblastic anemia.  

Demyelination is a feature of the condition with progressive neurological deficits, including peripheral neuropathy, loss of spinal reflexes, and poor vibrational and proprioception sense. End stage chronic hypocobalaminemic cases may exhibit dementia, and even frank psychosis. 

Myelosuppression is a common sequela of hypocobalaminemia due to the key role of vitamin B12 in DNA synthesis. Megaloblastic anemia is the commonest result of this. 

CNS disease is potentially the most serious manifestation, with the demyelination leading to subacute combined degeneration of the spinal cord (SACD).

There are significant stores of vitamin B12 (cobalamin) in the hepatocytes meaning that symptoms may not become evident for up to a decade after biochemical depletion first occurs.

The effects of insufficient cobalamin levels are the result of cellular inability to perform three metabolic reactions: 

  1. methylmalonic acid to succinyl coenzyme A
  2. homocysteine to methionine
  3. 5-methyltetrahydrofolate to tetrahydrofolate
  • Crohn disease
  • resection of ileum
  • infective ileitis e.g. tapeworm
  • transcobalamin II deficiency: transcobalamin is a carrier molecule for B12 in the plasma
  • alcohol excess
  • >75 years
  • vegans/fastidious vegetarians 
  • H2 histaminergic antagonists (e.g. ranitidine) for >1 year
  • metformin for >4 months
  • proton pump inhibitors (PPIs) for >1 year

In established hypovitaminosis B12 the main findings are of subacute combined degeneration of the spinal cord (SACD).

The mainstay of treatment is vitamin B12 supplementation.

The neurological dysfunction starts to respond to treatment within seven days and there is usually complete resolution in three months. Unfortunately 6% of patients treated for subacute combined degeneration of the spinal cord are left with permanent residual functional deficit 2.

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Article information

rID: 63934
Synonyms or Alternate Spellings:
  • hypovitaminosis B12
  • Hydroxocobalamin deficiency
  • Hydroxycobalamin deficiency
  • Cobalamin deficiency
  • Hypocobalaminemia
  • Hypocobalaminaemia

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