Can Pernicious Anemia be Hereditary?

Illustration of DNA of Pernicious Anemia


Pernicious Anemia, also known as Biermer’s disease, is a rare type of anemia or blood disease in which the body is unable to properly make use of Vitamin B12, an important component for forming red blood cells, DNA synthesis, and neurological functions.
It is caused by a deficiency of vitamin B12. It is often hereditary which usually affects individuals with a family history of pernicious anemia, those with a history of autoimmune disorders in the endocrine, those with various immunoglobulin deficiencies such as multiple myeloma, and those of Scandinavian, North European, or North American descent. It also affects more women than men. The adult onset is the most common form of pernicious anemia and the diagnosis usually takes place at around 60 years of age.

Causes of Pernicious Anemia

  • Failure in the process of the digestive tract

Vitamin B12, also known as cobalamin, can be absorbed through the body by eating meat and dairy products which are both great sources of it. Pernicious anemia is not only caused by the lack of intake of these primary sources of vitamin B12. It is caused by a failure in the complex process that the digestive tract needs to go through in order to absorb vitamin B12.

  • Lack of Intrinsic Factor

In most cases of this disease, it is caused by the lack of intrinsic factor (IF), a gastric protein that is needed by the body to absorb vitamin B12. Without the intrinsic factor, vitamin B12 can’t be absorbed and a deficiency develops. Vitamin B12 from dietary sources are absorbed through the intestinal cells after it combines with the gastric intrinsic factor. For the small intestine to absorb vitamin B12, it is essential for the intrinsic factor to be produced by the cells that line a part of the stomach. Once the intrinsic factor combines with vitamin B12, they are both absorbed into the lowest part of the small bowel just before the small bowel enters the colon. The combination of vitamin B12 and the intrinsic factor will not be absorbed by the body if the small bowel is damaged or removed because of surgery. Individuals that require surgery to remove part of the small bowel because of certain conditions such as Crohn’s disease need to be tested for vitamin B12 deficiency and go through treatment as needed.

The lack of intrinsic factor can also be congenital which means that the intrinsic factor is already lacking at birth. This type of pernicious anemia is called congenital anemia when seen at birth or juvenile anemia which is seen before a child turns three years of age. Congenital and juvenile anemia are inherited as autosomal recessive traits. It can be brought about by a recessive gene wherein even if only one parent carries the abnormal gene for this disease, it can be passed along to a child. The gene that is responsible for anemia that is caused by intrinsic factor deficiency has been tracked to a site on chromosome 11 (11q13).

  • Genetic Mutations

Another possible cause of B12 deficiency is when an inherited genetic deficiency does not allow the combination of the intrinsic factor with vitamin B12. This genetic deficiency will prevent the absorption of vitamin B12 which can result in a biological B12 deficiency.

  • Cellular Intake Mutations

There are also several types of genetic mutations that hinder B12 metabolism inside the cells. Simply having one of these genetic mutations can cause a B12 deficiency. The gene that is responsible for anemia that is caused by the intestinal malabsorption of vitamin B12 has been tracked to locations on chromosome 10 (10p12.1) and chromosome 14 (14q32). A genetic disorder in the metabolism of vitamin B12 allows normal blood levels and the normal absorption of vitamin B12 through the intestines but it does not allow the cells to metabolize after the intake of vitamin B12. Different enzymes within the cell

  • Associated Autoimmune Endocrine Disorders

Aside from the lack of intrinsic factor in order to absorb vitamin B12, there are also other possible causes in the decreased absorption of vitamin B12 that are not so common.
These include increased metabolism of vitamin B12 through longstanding hyperthyroidism, malabsorption syndromes, chronic pancreatitis, and certain medications. Vitamin B12 deficiency in older people is usually caused by poor absorption of dietary B12.

  • Intrinsic Factor Mutations

Pernicious anemia is an autoimmune disorder. Autoimmune disorders occur when the antibodies, the body’s natural defenses against foreign organisms, attack healthy tissues for unknown and unexplainable reasons. In the case of this disease, the body destroys the gastric intrinsic factor-producing cells. Pernicious anemia can sometimes link with autoimmune endocrine disorders like hypoparathyroidism, diabetes, Graves’ disease, testicular dysfunction, and Addison’s disease because pernicious anemia is frequently seen in combination with these disorders.

  • Family History

This disorder tends to affect certain families with more frequency compared to others that’s why it is possible that there might be a hereditary or genetic factor to pernicious anemia. That’s where there is a risk factor in individuals with a family history of pernicious anemia, those with a history of autoimmune disorders, and those of North European, North American, or Scandinavian descent.

  • Transcobalamin Mutations

Transcobalamin is a protein in the blood that combines with vitamin B12. It helps move vitamin B12 to all the cells in the body. If an individual has a genetic mutation that does not allow the development of transcobalamin, the cells will not be able to receive vitamin B12 which can result in a deficiency. There are also genetic mutations that can allow the development of transcobalamin but they prevent the absorption by the cells which also results in a B12 deficiency. This condition is rare and can be fatal after birth.

Pernicious anemia is thought of as an autoimmune disorder but there are certain individuals who have a genetic predisposition to this disease. Vitamin B12 deficiency can sometimes be caused by an inherited genetic disorder as explained in the various causes of the disease. In order to determine Vitamin B12 deficiencies that are caused by inherited genetic disorders, an individual needs to have a proper diagnosis from the doctor and the doctor may also possibly recommend a genetic testing. Most of the conditions affecting the absorption or metabolism of vitamin B12 have been associated with various gene mutations wherein a person only needs one mutation to experience vitamin B12 deficiency.