Pernicious anemia (PA) is a form of anemia caused by a functional deficiency of vitamin B-12, also known as cobalamin. Proper intestinal absorption of B-12 requires the presence of an intrinsic factor. Congenital pernicious anemia is a rare condition where PA sets in even in the presence of adequate consumption of B-12, due to a significantly decreased level of the intrinsic factor. Congenital PA is indicated by an early onset and the presence of similarly affected siblings. The acquired form, on the other hand, has its onset later in life. Atrophic gastritis and certain autoimmune conditions are known to precipitate acquired PA. The signs and symptoms of PA begin very slowly and may go unnoticed for a long time before diagnosis. These features include diarrhea or constipation, fatigue, loss of appetite, pale skin, lack of concentration, shortness of breath, and bleeding gums. In severe cases, nervous system damage may result in confusion, depression, and numbness in fingers and toes. The condition is most common in people of North European ancestry, while it is rarer in people of Asian or African origin.
Tests used to confirm a suspected diagnosis of the condition include blood tests, Schilling's test to check for vitamin B-12 absorption, and occasionally, bone marrow biopsy. Treatment involves administering vitamin B-12, orally or by way of injections. This treatment needs to be continued lifelong, since PA is currently incurable. Prognosis is excellent if treatment is started early. However, permanent nerve damage can ensue if treatment is not started within six-months of appearance of the nervous symptoms.
Epidemiological evidence, including familial clustering of the condition points to pernicious anemia as having a significant heritable component. This observation is supported by the fact that PA tends to co-occur with other autoimmune diseases. In congenital PA, autoantibodies directed against the Intrinsic Factor lead to a deficiency of the protein, resulting in malabsorption of B12. Genetic factors may play a role in the pathogenesis of adult-onset forms of the condition too. While the absolute cause is unknown, there are two major hypotheses; firstly PA is a defect in immunological tolerance to a particular antigen found in the stomach, thyroid gland, pancreas, and skin; and second it is a defect in a metabolic pathway that is common to these tissues. The disease has also been found in patients that have deletions in chromosome 18. These are associated with selective IgA deficiencies.