Vitamin B12 deficiency

A common cause of macrocytic anemia, pancytopenia, paresthesia, peripheral neuropathy, demyelination of the corticospinal tract and dorsal columns, psychiatric disorders, impaired memory, irritability, dementia and depression.

Vitamin B12 deficiency is common, affecting between 1.5% and 15% of the general population.


]In many of these cases, the cause of the vitamin B12 deficiency is unknown.

Vitamin B12 is essential for normal hematpoietic cellular maturation.

Maybe associated with glossitis, infertility, malabsorption, and thrombosis.

Gastric acid is required for the release of vitamin B 12 from dietary proteins to facilitate absorption in the terminal ileum.

Severe deficiency may cause peripheral sensory nerve damage and posterior and lateral column degeneration, subacute combined degeneration of the spinal cord.

Neuronal damage will progress if the deficiency is not corrected and go from demyelination to axonal degeneration and eventually neuronal death.

Neurologic symptoms, most commonly paresthesias, often precede hematologic abnormalities such as macrocytic anemia or hypersegmented neutrophils.

B12 deficiency can result in demyelinization of the cervical, thoracic and lateral columns of the spinal cord and occasionally cranial and oeripheral nerves and also of white matter can be involved.

Pathologically demyelinization appears as spongy degeneration with the loss of and swelling of myelin sheath and this abnormality can be visible on MRI imaging.

Impaired red blood cell maturation in the bone marrow leads to megaloblastic anemia.

In severe B 12 deficiency intramedullary hemolysis with leukocyte and megakaryocyte destruction leads to high LDH level, low haptoglobin level, and pancytopenia.

The severity of megaloblastic anemia is inversely correlated with the degree of neurologic dysfunction.

Recognition and treatment of vitamin B12 deficiency is essential to cause reversal of bone marrow failure and of demyelinating nervous system disease.

Cobalamin is synthesized by microorganisms, and is present in trace amounts in mostly foods of animal origin.

The interaction between folate and B12 is responsible for megaloblastic anemias is seen in both vitamin deficiencies.

The dyssynchrony between the maturation of cytoplasm and that of nuclei leads to macrocytosis, immature nuclei, and hypersegmentation of granulocytes in the peripheral blood.

Ineffective erythropoiesis results in intramedullary hemolysis and release of LDH.

Vitamin B12 is needed for the development and initial myelinization of the CNS, as well as for the maintenance of its normal functions.

Bone marrow hypercellularity and dysplastic changes can be mistaken for acute leukemia.

Incidence increases with age with 15% of adults older than 65 years having laboratory evidence of B12 deficiency.

Approximately 15% of persons over the age of 60 have undiagnosed B12 deficiency.

Estimated 3.2% of adults older than 50 years have a low serum B12 levels.

Present in 10-20% of elderly men and women, whereas less than 10% of such patients have anemia attributable to B12 deficiency.

Uptake in the G.I. tract depends on intrinsic factor, which is synthesized by gastric parietal cells and on the cubam receptor in the distant ileum.

About 7% of adults have subclinical cobalamin (B12) deficiency.

Can begin as early as 1 year after total gastrectomy.

Food-B12 malabsorption common among patients with atrophic gastritis, reduced acid secretion, such as with long-term use of acid suppressive therapy, partial gastrectomy, or vagotomy.

Following ingestion vitamin B12 initially binds to proteins carriers and then in the acidic environment of the stomach it dissociates from its protein carriers.

Intrinsic factor is manufactured by the parietal and zymogenic cells in the gastric fundus and body and binds to the free vitamin B 12 in the duodenum.

Binds to a glycoprotein, intrinsic factor, which is derived from the gastric mucosa.

The intrinsic factor-vitamin B 12 complex is eventually absorbed by receptors in the terminal ileum.

Disturbance in any of the process above can lead to B12 deficiency.

Malabsorption of vitamin B12 can occur in patients who lose their ileal receptors, such as with inflammatory bowel disease, or have their terminal ileum resected.

Malabsorptive B12 deficiency includes autoimmune pernicious anemia,, gastric surgery for obesity and ileum disease and or resection, as with inflammatory bowel disease.

When absorption of vitamin B12 is in question lifelong parenteral B12 therapy is chosen rather than oral-B12 therapy.

In malabsorption B12 deficiency essentially no B12 can be absorbed by the oral route.

Dietary insufficiency is a rare cause.

Bacterial overgrowth syndromes and D latum infestations can lead to vitamin B12 deficiencies.

Produces hyperhomocysteinemia, an independent risk factor for cardiovascular disease.

Thrombosis may be increased and is attributed to hyperhomocystinemia seen in severe vitamin B12 deficiency.

Leads to an increased methylmalonic acid level.

Folic acid supplementation may mask vitamin B12 deficiency.

Hyperpigmentation may occur owing to increased melanin synthesis and is seen in patients with darker skin and vitamin B 12 deficiency and is rapidly reversible with treatment.

With true tissue B12 deficiency elevations of homocystine more than 25 µmol per liter and methylmalonic acid to levels higher than 1000 nmol per liter are corroborative for tissue B12 deficiency.

Presently methylmalonic acid is the most sensitive and specific assay to diagnose B12 deficiency.

Folate acid made improved anemia but not prevent progression of neurologic symptoms in vitamin B12 deficiency.

Use of gastric acid-blocking agents lead to decreased B12 levels.

Measurement of methylmalonic acid and homocysteine levels are more sensitive in the diagnosis of B12 deficiency than measurement of serum B12 levels alone.

98.4% have elevated serum methylmalonic acid level and 95.9% have elevated serum homocysteine levels.

Paresthesias occur with vitamin B12 deficiency but not with folate deficiency.

In elderly patients associated with a depressive disorder.

Methylmalonic acid is not elevated in folate deficiency.

About 28% have normal hematocrit levels and 17% have normal mean corpuscular volumes.

Treatment involves regular intramuscular B12 injections.

Oral crystalline cyanocobalamin may be effective for treating food-B12 malabsorption.

Approximately 50% of patients have residual neurologic disease despite B-12 treatment.

Following treatment for a vitamin B12 deficiency potassium levels should be monitored because potassium is consumed during erythropoiesis and this can lead to life threatening hypokalemia.

Vitamin B12 levels may be falsely normal in patients with liver disease, myeloproliferative diseases, nitrous oxide exposure and methylmalonic acid and homocysteine levels should be checked to confirm the diagnosis.

Some patients with pernicious anemia can have enterochromaffin cell hyperplasia with hypergastrinemia and development of gastric carcinoid tumors.

1-7% of patients with pernicious anemia develop gastric carcinoid tumors.

An infant of mother with vitamin B 12 deficiency may be born with such a deficiency, or it may occur if the infant is exclusively breast-fed usually between 4-6 months of age.

B12 deficiency manifests in children with failure of brain development, impaired growth and development, developmental regression, feeding difficulties, lethargy, hypotonia, tremors, hyperirritability and coma.

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