What about the neurological system?

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

Renal (kidney)

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.

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