Congenital Deficiency of Intrinsic Factor - Causes, Diagnosis, and Treatment

Introduction

Intrinsic factor (IF) is a protein required to absorb vitamin B12, produced by the stomach lining's parietal cells (which are epithelial in origin). Intrinsic factor (IF) is a glycoprotein (a compound consisting of polysaccharides and protein components) secreted into the stomach. The other synonyms of intrinsic factor include gastric intrinsic factor (GIF) and cyanocobalamin (CO- 60).

What Is Congenital Deficiency of Intrinsic Factor?

Congenital intrinsic factor deficiency is a genetically inherited medical condition present from birth. It is caused by either deficiency or the absence of intrinsic factors. Intrinsic factor is necessary to absorb vitamin B12 (cobalamin) in the intestine. Vitamin B12 helps in red blood cell production, the synthesis of DNA (deoxyribonucleic acid), and the proper functioning of the nervous system. Lack of vitamin B12 may lead to anemia (a condition that develops due to low levels of red blood cells) as the body cannot produce red blood cells.

What Causes Congenital Deficiency of Intrinsic Factor?

Congenital intrinsic factor deficiency is mainly caused by congenital pernicious anemia and neurological abnormalities. This condition develops due to genetic mutation (a change in one or more genes in the DNA sequence) in GIF (gastric intrinsic factor gene) located on chromosome 11. It is an example of autosomal recessive inheritance. Autosomal recessive inheritance is a genetic disorder that can be inherited and passed down through multiple generations. It can occur when a child inherits the abnormal gene from both parents. If the child inherits only one copy of the abnormal gene, the child will be a carrier of this condition and have no symptoms.

What Are the Risk Factors for Deficiency of Intrinsic Factor?

Since it is an inherited medical condition, it mostly runs in families with a positive medical history. Other risk factors include:

• Surgical removal of the stomach, intestine, or part of them, can disrupt the body's ability to absorb vitamin B12.

• Autoimmune diseases such as type 1 diabetes.

• Crohn's Disease: It is a form of inflammatory bowel disease. An inflammatory bowel disease is a group of disorders that are caused by the inflammation of the digestive tract (the digestive tract is the route through which food enters the body and waste is eliminated).

• HIV (human immunodeficiency virus): A virus that attacks the immune system and weakens an individual's defense against the infection.

• Pure vegetarians are at higher risk due to a lack of vitamin B12 in plant-based food sources.

What Are the Symptoms of Congenital Deficiency of Intrinsic Factor?

Most cases of congenital deficiency of intrinsic factor develop before the age of five years. The signs and symptoms of this condition mimic vitamin B12 deficiency. The signs and symptoms seen in the mild case include:

• Pale skin (yellowing of eyes or skin).

• Loss of appetite.

• Dyspnea (shortness of breath), especially during exercise.

• Heartburn.

• Diarrhea (loose stools) or constipation.

• Swollen, reddish tongue or bleeding gums.

• Lightheadedness while standing.

Long-term cases of congenital deficiency of intrinsic factor can cause neurological symptoms, which include:

• Memory loss: It is usually short-term.

• Confusion.

• Depression.

• Loss of balance.

• Tingling and numbness may be present in the extremities.

• Vision loss occurs in some cases due to damage to the optic nerve.

• Irritability.

How Can Congenital Deficiency of Intrinsic Factor Be Diagnosed?

The congenital deficiency of intrinsic factor can be diagnosed based on detailed history taking, physical examination, identification of characteristic findings, and various blood tests. In physical examination, the healthcare professionals check for signs of anemia (a condition due to low levels of healthy red blood cells), including weakness, fatigue, and pale skin. They may also check other symptoms like weight loss and problems related to digestion. Finally, blood tests are usually performed to confirm the diagnosis, which includes:

• Complete Blood Count (CBC): This blood test is done to find the type of anemia.

• Lactate Dehydrogenase (LDH) Levels: This enzyme level is highly elevated in anemia cases.

• Methylmalonic Acid (MMA) Levels: MMA levels are high in case of vitamin B12 deficiency.

• Homocysteine Level: The level of homocysteine (a naturally occurring amino acid) is high due to vitamin B12 deficiency.

• Intrinsic Factor Antibody Test: This blood test is performed to identify antibodies present in response to the absence of intrinsic factor.

• Vitamin B12 Level: It measures the amount of vitamin B12 in the blood or urine.

• Serum Bilirubin Levels: Bilirubin is a yellow color pigment formed as a result of red blood cell break down).

• Reticulocyte Count: Reticulocyte is an immature form of red blood cells.

Additional tests include:

• Schilling Test: This test is done to determine the ability of the body to absorb vitamin B12. It involves drinking a solution with radioactive vitamin B12 followed by assessing vitamin B12 levels in the urine.

• Gastric Analysis: This method involves taking a small tissue sample from the stomach and testing the sample for evidence of intrinsic factor.

• Endoscopic Examination: This procedure is performed by inserting a thin tube with a camera at one end through the mouth and into the stomach. Healthcare professionals look for any abnormalities in the stomach that may lead to intrinsic factor deficiency.

How Can Congenital Deficiency of Intrinsic Factor Be Treated?

The objective of the treatment is to restore the vitamin B12 level in the body. The duration and the mode of treatment depend on the cause of the deficiency. Intramuscular injections of vitamin B12 are prescribed weekly or monthly in the standard treatment routine. Hydroxocobalamin injections are also advised over cyanocobalamin which can cause muscular pain and neurological side effects. Oral vitamin B12 supplementation is often not suggested as it is ineffective. A special diet rich in vitamin B12 should be followed in the later phases of treatment.

What Are the Possible Complications of Congenital Deficiency of Intrinsic Factor?

One of the critical complications of congenital deficiency of intrinsic factor is gastric cancer (abnormal growth of cells in the stomach). The symptoms of this cancer can be monitored by a healthcare professional with the help of imaging tests and biopsy. Other complications include peripheral nerve damage, digestive tract problems, and heart-related problems. However, these complications often occur only in long-lasting cases of vitamin B12 deficiency.

Conclusion

Congenital deficiency of intrinsic factor is a genetically inherited health condition in which the person cannot produce intrinsic factor. It is not considered a life-threatening condition, but the treatment has to be started at the earliest to avoid significant complications like nerve damage. Even though it is impossible to cure this permanently, we can reduce the symptoms and its complications by supplementing vitamin B12 into the body. Since this is a life-long supplementation process, it is necessary to be continuously monitored by a healthcare professional.