What about the neurological system?

What are the two key organ systems affected by vitamin B12 deficiency?

Neurological manifestations .

• Due to defective initiation and maintenance of central and peripheral neuron myelination
• They include:
  • Sensory deficits and weakness (from peripheral neuropathy) – secondary to sensory and motor neuron myelination
  • Difficulty with gait/ataxia (from subacute combined degeneration of spinal cord):
    • Also called demyelinating neurological disease.
    • Involves demyelination of the posterior and lateral tracts which contain sensory neurons that are involved in conduction of vibration and position, are especially susceptible to demyelination.
    • If left untreated, may progress to axonal degeneration and neuronal death with disturbances of proprioception, vibratory sense, and areflexia; usually, improvement will not continue past 1 year of sufficient treatment.
  • Autonomic dysfunction
  • Optic neuropathy:
    • Optic neuritis
    • Optic atrophy

Neuropsychiatric manifestations include:

• Memory impairment
• Dementia
• Depression

Mechanisms of neurological complications:

• Methylcobalamin is a cofactor for methionine synthase in a methyl-transfer reaction that converts homocysteine to methionine. Methionine is adenosylated to S-adenosylmethionine, a methyl group donor required for neuronal methylation reactions. Decreased S-adenosylmethionine production leads to reduced myelin basic protein methylation.
• Cobalamin is a cofactor for mitochondrial L-methylmalonyl coenzyme A (CoA) mutase, which catalyzes the conversion of L-methylmalonyl CoA to succinyl CoA. Accumulation of methylmalonate and propionate provides abnormal substrates for fatty acid synthesis.

Neurological involvement:

• May be the earliest and only manifestation of vitamin B12 deficiency.
• May appear due to vitamin B12 deficiency in the presence of a normal hemoglobin (Hb) and mean cell volume (MCV) (about one-quarter patients present without anemia).
• For unclear reasons, severity of neurological presentation inversely correlated with severity of hematological findings.

Our patient had no evidence of neurological involvement.