The cobalamins, also referred to as vitamin B12, are a group of closely related enzymatic cofactors involved in the synthesis of methionine from homocysteine. Vitamin B12 deficiency can lead to megaloblastic anaemia and neurological deficits. Unfortunately, many other conditions 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 anaemia, which possibly is the commonest type of cobalamin deficiency in developed countries, require either massive doses of oral vitamin B12 or parenteral replacement therapy.
That is because pernicious anaemia patients suffer from 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 intrinsic factor binds the free vitamin B12, carries it to receptors on the ileal mucosa, and facilitates its absorption.
Most pernicious anaemia patients have autoantibodies against gastric parietal cells or intrinsic factor, with the latter being very specific but only present in approximately 50% of cases. By contrast, parietal cell antibodies (PCA) are found in approximately 90% of patients with pernicious anaemia, but are also found in a significant proportion of patients suffering from other autoimmune diseases. Moreover, these antibodies can be detected in approximately 2.5% of healthy individuals in the fourth decade of life to approximately 10% of healthy individuals in the eighth decade of life.