Clinical Information

The cobalamins, also referred to as vitamin B12, are a group of closely related enzymatic cofactors involved in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A and in the synthesis of methionine from homocysteine. Vitamin B12 deficiency can lead to megaloblastic anemia and neurological deficits. The latter may exist without, or precede, anemia. Adequate replacement therapy will generally improve or cure cobalamin deficiency. Unfortunately, many other conditions, which require different interventions, can mimic the symptoms and signs of vitamin B12 deficiency. Moreover, even when cobalamin deficiency has been established, clinical improvement may require different dosages or routes of vitamin B12 replacement, depending on the underlying cause. In particular, patients with pernicious anemia (PA), possibly the most common type of cobalamin deficiency in developed countries, require either massive doses of oral vitamin B12 or parenteral replacement therapy. This is due to patients with PA having gastric mucosal atrophy, most likely caused by a destructive autoimmune process. This results in diminished or absent gastric acid, pepsin, and intrinsic factor (IF) production. Gastric acid and pepsin are required for liberation of cobalamin from binding proteins, while IF binds the free vitamin B12, carries it to receptors on the ileal mucosa, and facilitates its absorption. Most PA patients have autoantibodies against gastric parietal cells or IF, with the latter being very specific but only present in approximately 50% of cases. By contrast, parietal cell antibodies are found in approximately 90% of PA patients, but are also found in a significant proportion of patients with other autoimmune diseases and in approximately 2.5% (4th decade of life) to approximately 10% (8th decade of life) of healthy individuals.