Vitamin B12 deficiency

Vitamin B₁₂ deficiency (or(also hypovitaminosisB₁₂ or hypocobalaminaemia) is not uncommon, with potentially serious sequelae if not adequately treated.

Clinical presentation

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 anaemia.  

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 hypocobalaminaemic cases may exhibit dementia, and even frank psychosis. 

Myelosuppression is a common sequela of hypocobalaminaemia due to the key role of vitamin B₁₂ in DNA synthesis. Megaloblastic anaemia 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).

Pathology

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

The effects of insufficient hydroxocobalamin 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

Aetiology

Insufficient intrinsic factor

• pernicious anemia: commonest cause globally of B12 deficiency
• atrophic gastritis
• gastrectomy: producing postgastrectomy syndrome
• genetic

Ileal malabsorption

• Crohn disease
• resection of ileum
• infective ileitis e.g. tapeworm

Genetic

• transcobalamin II deficiency

Nutritional

• alcohol excess
• >75 years
• vegans/fastidious vegetarians 

Pharmacological

• H₂ histaminergic antagonists for >1 year
• metformin for >4 months
• proton pump inhibitors (PPIs) for >1 year