Neurological Manifestations of Cobalamin Deficiency

Vitamin B12 (cobalamin) is synthesized by microorganisms and detected in trace amounts mostly in foods of animal origin. The absorption and transporting mechanisms depended on three key proteins: haptocorrin, intrinsic factor and transcobalamin. On the peripher cobalamin circulates only in binding with proteins transcobalamin I and II (holotranscobalamin). Holotranscobalamin is absorbed by different cells, whereas transcobalamin I-binded vitamin B12 -only by liver and kidneys. Two forms of cobalamin were identified as coenzymes of cellular reactions which are methylcobalamin and hydroxyadenosylcobalamin. The interaction between folate and B12 is responsible for the megaloblastic anemia seen in both vitamin deficiencies. Vitamin B 12 is necessary for the development and initial myelination of the central nervous system as well as for the maintenance of its normal function. Neurologic manifestations of B12 deficiency are polymorph. Causes are dominated by Pernicious anemia and B12 vitamin non dissociation that is frequent in the elderly. It is estimated that 40% of older adults have vitamin B12 deficiencies and most due to cobalamin malabsorption. Neurologic and psychiatic manifestations of B12 deficiency are rarely initial symptoms. They are usually attributed to the intervention of vitamin B12 in the isomerization reaction of Methylmalonic Acid (MMA) to succinic acid. Neurological involvement often occurs along with macrocytic anemia but can arise in the absence of either anemia or macrocytosis. Also, it is unclear why vitamin B12 deficiency leads to neurological disease in some patients and hematological disease in others. The well-known major manifestations described include peripheral neuropathy, subacute combined degeneration of spinal cord, dementia, optic atrophy, psychosis and mood disturbance. Other, neurological disorders also described are cerebellar ataxia, abnormalities of cranial nerves, Parkinsonian syndrome and movement disorders. Substitutive vitamin therapy is required when diagnosis is strongly suspected, and etiologic assessment is negative. High-dose oral vitamin B12 tablets (1000 to 2000 g) taken daily are as effective as intramuscular monthly injections in correcting blood and neurologic abnormalities.