Pernicious anemia is thought to be an autoimmune disease. Autoimmune disorders are caused when the body’s natural defenses (e.g., antibodies) against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons. Pernicious anemia is sometimes seen in association with certain autoimmune endocrine diseases, such as type 1 diabetes, hypoparathyroidism, Addison’s disease, and Graves’ disease.

However, since the disorder also tends to occur with greater frequency in certain families than in others, it is also believed that there may be a genetic component to pernicious anemia. In general, risk factors for pernicious anemia include a family history of the disease, being of Northern European or Scandinavian descent, and a history of autoimmune endocrine disorders.

The congenital and juvenile forms are thought to be inherited as autosomal recessive traits. The gene responsible for anemia due to intrinsic factor deficiency has been tracked to a location on chromosome 11 (11q13). The gene responsible for anemia due to the intestinal malabsorption of vitamin B12 has been tracked to sites on chromosome 14 (14q32) and 10 (10p12.1).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11q13” refers to band 13 on the long arm of chromosome 11. Similarly gene map loci 14q32 and 10p12.1 refer to a site at band 32 on the long arm of chromosome 14, and at band 12.1 on the short arm of chromosome 10. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.