Congenital pernicious anemia
Pernicious anemia is caused by a lack of intrinsic factor, a substance needed to absorb vitamin B12 from the gastrointestinal tract. Vitamin B12 is necessary for the formation of red blood cells.
Anemia is a condition where red blood cells are not providing adequate oxygen to body tissues. There are many types and causes of anemia. See also: Anemia.
Pernicious anemia is a type of megaloblastic anemia.
Macrocytic achylic anemia; Congenital pernicious anemia; Juvenile pernicious anemia; Vitamin B12 deficiency (malabsorption)
Intrinsic factor is a protein that helps the body absorb vitamin B12. When stomach secretions do not have enough intrinsic factor, vitamin B12 is not absorbed well. This results in pernicious anemia and other problems related to low levels of vitamin B12.
Nerve and blood cells need vitamin B12 to function properly, so deficiency can cause a wide variety of symptoms, including fatigue, shortness of breath, tingling sensations, difficulty walking, and diarrhea.
Other causes of low levels of intrinsic factor (and thus of pernicious anemia) include atrophic gastric mucosa, autoimmunity against gastric parietal cells, and autoimmunity against intrinsic factor.
Absence of intrinsic factor itself is the most common cause of vitamin B12 deficiency. Intrinsic factor is produced by cells in the stomach. In adults, the inability to make intrinsic factor can be the result of chronic gastritis or the result of surgery to remove the stomach. The onset of the disease is slow and may take decades.
Very rarely, infants and children are born lacking the ability to produce effective intrinsic factor. This form of congenital (born with) pernicious anemia is inherited as an autosomal recessive disorder (you need a defective gene from each parent to get it). Most often, however, pernicious anemia and other forms of megaloblastic anemia in children results from other causes of vitamin B12 deficiency or other vitamin deficiencies.
Although a form of the disease can occur in children, pernicious anemia usually does not appear before age 30. The average age at diagnosis is 60. In fact, one recent study revealed that nearly 2% of individuals over 60 have pernicious anemia. Slightly more women than men are affected. The disease occurs in all racial groups, but occurs most often in people of Scandinavian or Northern European descent.
Risk factors include a family history of pernicious anemia, Scandinavian or Northern European descent, and a history of autoimmune endocrine disorders. Pernicious anemia is seen in association with some autoimmune endocrine diseases such as type 1 diabetes,hypoparathyroidism, Addison's disease, hypopituitarism, testicular dysfunction, Graves disease, chronic thyroiditis, myasthenia gravis, secondary amenorrhea, and vitiligo.
In addition to pernicious anemia, other causes of vitamin B12 deficiency include:
- Nutrition (strict vegetarians without B12 supplementation, poor diet in infant, or poor maternal nutrition during pregnancy)
- Infection (intestinal parasites, bacterial overgrowth)
- Gastrointestinal disease [stomach removal surgery, celiac disease (sprue), Crohn's disease]
- Drugs (colchicine, neomycin, tuberculosis treatment with para amino salicylic acid)
- Metabolic disorders (methylmalonic aciduria, homocystinuria)
Many cells in our body need vitamin B12, including nerve cells and blood cells. Inadequate vitamin B12 gradually affects sensory and motor nerves, causing neurological problems to develop over time. It is important to know that the neurological effects of vitamin B12 deficiency may be seen before anemia is diagnosed.
The anemia also affects the gastrointestinal system and the cardiovascular system. The following symptoms may indicate pernicious anemia:
- Shortness of breath
- Rapid heart rate
- Loss of appetite
- Tingling and numbness of hands and feet
- Sore mouth
- Unsteady gait, especially in the dark
- Tongue problems
- Impaired sense of smell
- Bleeding gums
- Positive Babinski's reflex
- Loss of deep tendon reflexes
- Personality changes, "megaloblastic madness"
Exams and Tests
Tests that may indicate pernicious anemia include:
- CBC results that show low hematocrit and hemoglobin with elevated MCV (low red blood cell count with large-sized red blood cells)
- CBC showing low white blood count and low platelets
- Low reticulocyte count
- Bone marrow examination (only needed if diagnosis is unclear)
- Serum LDH
- Below normal serum vitamin B12 level
- Schilling test
- Measurement of serum holotranscobalamin II
- Measurement of methylmalonic acid (MMA)
This disease may also alter the results of the following tests:
- Peripheral smear
- Leukocyte alkaline phosphatase
- Cholesterol test
Monthly vitamin B12 injections are the definitive treatment to correct the vitamin B12 deficiency. This therapy corrects the anemia and may correct the neurological complications if given soon enough.
Since about 1% of vitamin B12 is absorbed (even in the absence of intrinsic factor), some doctors recommend that elderly patients with gastric atrophy take oral vitamin B12 supplements in addition to monthly injections.
There is also a preparation of vitamin B12 that may be given intranasally (in the nose). A well-balanced diet is essential to provide other elements such as folic acid, iron, and vitamin C for healthy blood cell development.
The outcome is usually excellent with treatment.
- People with pernicious anemia may have gastric polyps and get gastric cancer and gastric carcinoid tumors twice as often than the normal population.
- Persistent neurological defects may be present if treatment is delayed.
- Vitamin B12 deficiency affects the appearance of all epithelial cells, therefore an untreated woman may obtain a false positive pap smear.
When to Contact a Medical Professional
Call your health care provider if symptoms suggestive of vitamin B12 deficiency develop.
Pernicious anemia is not preventable, but with early detection and treatment of vitamin B12 deficiency, complications are readily controlled.