Congenital intrinsic factor deficiency is a rare disorder caused by a mutation in the gene encoding gastric intrinsic factor (GIF).
Symptoms of congenital intrinsic factor deficiency are similar to those of vitamin B12 deficiency causing megaloblastic anemia as that is its chief identifiable manifestation. Often the patient is brought and misdiagnosed as being in a poor nutritional state.
All the signs noted for pernicious anemia and megaloblastic anemia can be noted here:
The mutated gene cannot be repaired so the primary course of treatment is supplementation. Oral supplementation of vitamin B12 is completely ineffective as it is not absorbed from the intestines, as explained above.
Injectable form of vitamin B12 – to the tune of 1,500 mcg per day over a period of time is advisable to bring up the vitamin B12 levels and maintenance of these levels by way of regular injectable supplements is the best known treatment [6].
Along with that folic acid, niacin and thiamine have also shown to help the nutritional deficiencies caused. In cases where the bone marrow is affected, bone marrow transplant and chemotherapy are called for.
Since this disorder is congenital and related to a mutation in the gene, there is nothing that can be done to reverse the mutated gene [4]. Due to pernicious anemia and megaloblastic anemia, there is failure to thrive and poor nutrition. This can be corrected with heavy supplementation of vitamin B12 and in mild to moderate cases the patient can survive for quite a long time based on these supplements.
As the name suggests, it is congenital or hereditary. There is a bi-allelic mutation found in the patients. This mutation occurs on the encoding of chromosome 11 codon sequence number 5 [1]. It causes absence of the enzyme that helps the glycoprotein GIF (Gastric intrinsic factor) break down the cobalamin and get absorbed through the small intestine. Studies have not yet been conducted on the parents or siblings of the patients to know about their involvement at the genetic level or the factors causing the mutation.
Very few cases of actual congenital intrinsic factor deficiency are known. World over there may be about 100 odd such cases of which only 50 have been documented with proper studies and research. The problem is that the manifestation is usually up to 4 years of age, but sometimes it can manifest as late as after the 1st decade or after the 3rd decades of life as well [2].
Another problem is that cases that are detected early in their life, come as failure to thrive and often the diagnosis does not lead to IFD as early as it should.
The gastric intrinsic factor (GIF) is present along with the hydrochloric acid in the stomach, as well as peptin. Though their amounts may vary, most often than not, HCl has some amount of GIF with it in the stomach. When vitamin B12 enters the stomach, first it gets bound to a glycoprotein called haptocorrin. Then in the duodenum, enzymes digest that haptocorrin and finally in the small intestine the intrinsic factor binds to the vitamin B12. In the absence of GIF, the B12 is not absorbed or bound well and since it is water soluble, it gets wasted [3]. The deficiency of vitamin B12 then causes pernicious anemia or megaloblastic anemia.
Being a congenital disorder of possible genetic mutation, there is no available method of prevention.
Intrinsic factor deficiency or (IFD) is quite a well known and prevalent disorder, but congenital intrinsic factor deficiency or hereditary intrinsic factor deficiency is quite rare and only a few cases are known worldwide.
Essentially, intrinsic factor is a protein found in the acid secreted by the stomach which allows breakdown and absorption of vitamin B12 (cobalamin) through the small intestine. Deficiency of this enzyme causes malabsorption of cobalamin and thus, leads to pernicious anemia or megaloblastic anemia in spite of adequate B12 consumption.
Congenital intrinsic factor deficiency occurs when the stomach fails to produce any intrinsic factor (IF) or produces defective IF. This happens due to a genetic mutation and is therefore hereditary though there are no studies done on the parents of cases of congenital intrinsic factor deficiency, yet.
Often symptoms are noted in the first 5 years of life, if not, they can reveal themselves well after 10 years or during teenage. They reveal themselves disguised as symptoms of anemia – megaloblastic anemia commonly. This is because the absence of the intrinsic factor causes vitamin B12 deficiency (cobalamin) which leads to pernicious anemia or megaloblastic anemia in which red blood cells are larger than normal and therefore get destroyed easily. This leads to poor nutrition for the child and child does not put on weight or grow or gain as he should. This can also be associated with frequent episodes of diarrhea, enlarged liver and spleen and on the mental plane – one may note weakness, lack of concentration and irritability. Most milestones will also be delayed, if not significantly.
The best known treatment for this is vitamin B12 supplementation – by synthetically prepared vitamin B12. Unfortunately this cannot be administered orally and must be taken as an injectable for best results.