GeneHealth - Your precision medicine

Pernicious Anemia

Disease Details

Family Health Simplified

Buy Membership

Description: Pernicious anemia is an autoimmune condition where the body cannot absorb enough vitamin B12 due to a lack of intrinsic factor, leading to a decrease in red blood cells.
Type: Pernicious anemia is primarily an autoimmune disorder. It is not typically classified as a genetic disease, but there can be a familial predisposition, suggesting some genetic component may be involved. However, the exact mode of genetic transmission is not well established.
Signs And Symptoms: Pernicious anemia often presents slowly, and can cause harm insidiously and unnoticeably. Untreated, it can lead to neurological complications, and in serious cases, death. The onset may be vague and slow and the condition can be confused with other conditions, and there may be few to many symptoms without anemia. Pernicious anemia may be present without a person experiencing symptoms at first, over time, feeling tired and weak, lightheadedness, dizziness, headaches, rapid or irregular heartbeat, breathlessness, glossitis (a sore red tongue), poor ability to exercise, low blood pressure, cold hands and feet, pale or yellow skin, easy bruising and bleeding, low-grade fevers, tremor, cold sensitivity, chest pain, upset stomach, nausea, loss of appetite, heartburn, weight loss, diarrhea, constipation, severe joint pain, feeling abnormal sensations including tingling or numbness to the fingers and toes (pins and needles), and tinnitus, may occur. Anemia may present with a number of further common symptoms, including hair thinning and loss, early greying of the hair, mouth ulcers, bleeding gums, angular cheilitis, a look of exhaustion with pale and dehydrated or cracked lips and dark circles around the eyes, as well as brittle nails.In more severe or prolonged cases of pernicious anemia, nerve cell damage may occur. This is may result in sense loss, difficulty in proprioception, neuropathic pain, difficulty walking, poor balance, loss of sensation in the feet, muscle weakness, blurred vision (either due to retinopathy or optic neuropathy), impaired urination, fertility problems, decreased sense of taste and smell, decreased level of consciousness, changes in reflexes, memory loss, mood swings, depression, irritability, cognitive impairment, confusion, anxiety, clumsiness, psychosis, and, in more severe cases, dementia. Anemia may also lead to cardiac murmurs and/or altered blood pressure (low or high). The deficiency may also present with thyroid disorders. In severe cases, the anemia may cause congestive heart failure. A complication of severe chronic PA is subacute combined degeneration of spinal cord, which leads to distal sensory loss (posterior column), absent ankle reflex, increased knee reflex response, and extensor plantar response. Other than anemia, hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Vitamin B12 deficiency, which is reversible, is occasionally confused with acute myeloid leukemia, which is an irreversible condition presenting with some of the same hematological symptoms, including hypercellular bone marrow with blastic differentiation and hypersegmented neutrophils. Pernicious anemia can cause osteoporosis and may lead to bone fractures. Pernicious anemia can contribute to a delay in physical growth in children, and may also be a cause for delay in puberty for adolescents.
Prognosis: A person with well-treated PA can live a healthy life. Failure to diagnose and treat in time, however, may result in permanent neurological damage, excessive fatigue, depression, memory loss, and other complications. In severe cases, the neurological complications of pernicious anemia can lead to death – hence the name, "pernicious", meaning deadly.There is an increased risk of gastric cancer in those with pernicious anemia linked to the common feature of atrophic gastritis.
Onset: Pernicious anemia typically has a gradual onset. It often develops slowly over several months or years.
Prevalence: The prevalence of pernicious anemia is estimated to be approximately 0.1% in the general population and about 1.9% in people older than 60 years. This condition is more common in individuals of Northern European descent.
Epidemiology: PA is estimated to affect 0.1% of the general population and 1.9% of those over 60, accounting for 20–50% of B12 deficiency in adults. A review of literature shows that the prevalence of PA is higher in Northern Europe, especially in Scandinavian countries, and among people of African descent, and that increased awareness of the disease and better diagnostic tools might play a role in apparently higher rates of incidence.
Intractability: Pernicious anemia is not considered intractable. It can be managed effectively with proper treatment, primarily through lifelong vitamin B12 supplementation, either via injections or high-dose oral supplements. Early diagnosis and ongoing management are crucial for controlling the disease and preventing long-term complications.
Disease Severity: Pernicious anemia is a chronic condition that can be severe if left untreated. It results from the body's inability to absorb vitamin B12 due to a lack of intrinsic factor, a protein needed for vitamin B12 absorption in the intestines. This deficiency can lead to serious complications, including neurological problems, cardiovascular issues, and other systemic symptoms. Early diagnosis and ongoing treatment with vitamin B12 supplementation can effectively manage the condition and prevent severe complications.
Healthcare Professionals: Disease Ontology ID - DOID:13381
Pathophysiology: Although the healthy body stores three to five years' worth of B12 in the liver, the usually undetected autoimmune activity in one's gut over a prolonged period of time leads to B12 depletion and the resulting anemia; pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12. The body needs enough intrinsic factor to absorb and reabsorb vitamin B12 from the bile, in which reduces the time needed to develop a deficiency.B12 is required by enzymes for two reactions: the conversion of methylmalonyl-CoA to succinyl-CoA, and the conversion of homocysteine to methionine. In the latter reaction, the methyl group of levomefolic acid is transferred to homocysteine to produce tetrahydrofolate and methionine. This reaction is catalyzed by the enzyme methionine synthase with B12 as an essential cofactor. During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of levomefolic acid. This accumulation depletes the other types of folate required for purine and thymidylate synthesis, which are required for the synthesis of DNA. Inhibition of DNA replication in maturing red blood cells results in the formation of large, fragile megaloblastic erythrocytes. The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl- CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl-CoA mutase.
Carrier Status: Pernicious anemia is not typically described in terms of "carrier status" as it is primarily an autoimmune condition rather than a genetic disorder inherited in a simple Mendelian fashion. It results from the body's inability to absorb vitamin B12 due to the destruction of stomach cells that produce intrinsic factor, which is crucial for B12 absorption. There is a genetic predisposition, but no defined "carrier status."
Mechanism: Pernicious anemia is primarily caused by the body's inability to absorb vitamin B12 due to a lack of intrinsic factor, a protein secreted by the stomach lining. Intrinsic factor is essential for vitamin B12 absorption in the small intestine.

Molecular Mechanisms:
1. **Autoimmune Response**: The most common cause of pernicious anemia is an autoimmune reaction wherein the body's immune system produces antibodies that attack the parietal cells in the stomach lining, which produce intrinsic factor, or the intrinsic factor itself. This reduces or eliminates intrinsic factor production.

2. **Disruption of Vitamin B12 Absorption**: Without sufficient intrinsic factor, vitamin B12 cannot bind and be absorbed in the ileum (the last part of the small intestine). Vitamin B12 is crucial for DNA synthesis and the formation of red blood cells.

3. **Impact on DNA Synthesis**: Vitamin B12 is a cofactor for the enzyme methionine synthase, which is involved in the methylation cycle necessary for DNA synthesis. A deficiency in vitamin B12 disrupts this cycle, leading to impaired DNA synthesis and the production of large, immature red blood cells known as megaloblasts.

4. **Neurological Effects**: Vitamin B12 is also critical for the maintenance of the myelin sheath that insulates nerve fibers. Its deficiency can lead to neurological symptoms and nerve damage.

Overall, the autoimmune destruction of intrinsic factor or the gastric parietal cells, coupled with subsequent impaired vitamin B12 absorption, leads to the hematological and neurological manifestations of pernicious anemia.
Treatment: Pernicious anemia is usually easily treated by providing the necessary level of vitamin B12 supplementation. Pernicious anemia can be treated with intramuscular injections of vitamin B12. Initially in high daily doses, followed by less frequent lower doses, as the condition improves. Activity may need to be limited during the course of treatment. As long as the body is saturated with vitamin B12 expected to result in cessation of anemia-related symptoms and there are no other symptoms, unless there are irreversible neurological complications. There are not enough studies on whether pills are as effective in improving or eliminating symptoms as parenteral treatment. Folate supplementation may affect the course and treatment of pernicious anemia if vitamin B12 not replaced. In some severe cases of anemia, a blood transfusion may be needed to resolve haematological effects. Treatment is lifelong.The treatment of PA varies by country and area. Opinions vary over the efficacy of administration (parenteral/oral), the amount and time interval of the doses, or the forms of vitamin B12 (e.g. cyanocobalamin/hydroxocobalamin). More comprehensive studies are still needed in order to validate the feasibility of a particular therapeutic method for PA in clinical practices.
Compassionate Use Treatment: Compassionate use or experimental treatments for pernicious anemia primarily focus on investigational therapies being considered when standard treatments are ineffective or not suitable. However, current well-established treatments such as vitamin B12 supplementation are generally quite effective. Off-label or experimental treatments might include:

1. **Alternative Routes of B12 Administration**: Investigational efforts might explore different formulations or delivery methods of vitamin B12, such as nasal sprays or transdermal patches, although these are not standard treatments.

2. **Gene Therapy**: Future potential treatments could involve gene therapy to address the underlying genetic causes of vitamin B12 absorption issues, though this is still largely theoretical and experimental.

3. **Folic Acid Supplementation**: While not a standard treatment for pernicious anemia, folic acid supplements might be used to address additional anemia symptoms, though it does not correct the underlying B12 deficiency.

4. **Immune Modulating Therapies**: Given the autoimmune nature of pernicious anemia, some experimental approaches might consider immunomodulatory treatments to reduce the autoimmune attack on gastric cells that produce intrinsic factor.

Always consult a healthcare provider for information on the most appropriate and current treatments for pernicious anemia.
Lifestyle Recommendations: For pernicious anemia, here are some lifestyle recommendations:

1. **Dietary Adjustments**:
- Increase intake of foods rich in Vitamin B12 such as meat, fish, dairy products, and fortified cereals.
- For vegetarians or vegans, focus on fortified foods and supplements since plant-based foods don't naturally contain B12.

2. **Regular Medical Check-Ups**:
- Schedule routine blood tests to monitor B12 levels and overall blood health.
- Follow your healthcare provider's treatment plan which may include Vitamin B12 injections or oral supplements.

3. **Healthy Lifestyle**:
- Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins.
- Stay hydrated and engage in regular physical activity to boost overall health and energy levels.

4. **Avoid Smoking and Limit Alcohol**:
- Smoking and excessive alcohol consumption can interfere with nutrient absorption and overall health.

5. **Educate Yourself**:
- Learn about pernicious anemia to better manage the condition and recognize early symptoms of low B12 levels.

6. **Manage Other Health Conditions**:
- If you have other autoimmune disorders or gastrointestinal issues, work with your healthcare provider to manage these, as they can impact B12 absorption.

7. **Stress Management**:
- Engage in stress-reducing activities such as yoga, meditation, or hobbies to promote overall well-being.

Making these adjustments can help manage pernicious anemia and improve quality of life.
Medication: Pernicious anemia is typically treated with vitamin B12 supplementation. This can be administered through intramuscular injections or high-dose oral B12 supplements. The specific regimen depends on the severity of the deficiency and the patient's response to treatment. Regular monitoring of B12 levels and blood counts is essential to ensure effective management.
Repurposable Drugs: There are no well-established repurposable drugs for pernicious anemia. The primary treatment involves addressing the underlying vitamin B12 deficiency, typically through vitamin B12 injections or high-dose oral supplements. Research into new treatment strategies continues, but as of now, management relies on correcting the deficiency and monitoring the patient's response.
Metabolites: Pernicious anemia primarily results from vitamin B12 deficiency due to impaired absorption. This condition impacts several metabolic pathways. Key metabolites associated with pernicious anemia include:

1. **Methylmalonic Acid (MMA)**: Elevated levels of MMA indicate impaired vitamin B12-dependent enzymatic activity.
2. **Homocysteine**: Increased homocysteine levels can occur due to the disruption of the conversion to methionine, a process that requires vitamin B12.
3. **Lactate**: Elevated lactate levels can sometimes be noted due to impaired metabolism.

These metabolites can serve as markers to diagnose and monitor the treatment efficacy for pernicious anemia.
Nutraceuticals: Pernicious anemia can be supported with nutraceuticals such as:

1. **Vitamin B12**: The primary treatment, often administered as oral supplements or injections, since pernicious anemia is caused by a deficiency of this vitamin.
2. **Folic Acid**: Supports red blood cell production and can be taken as a supplement.
3. **Iron**: Although not directly related to pernicious anemia (which is a B12 deficiency), if anemia has led to iron deficiency, supplementation might be needed.
4. **Vitamin C**: Enhances iron absorption, which can be beneficial if iron supplementation is required.

Always consult with a healthcare provider before starting any new supplement regimen.
Peptides: Pernicious anemia is associated with a deficiency in intrinsic factor, which is crucial for the absorption of vitamin B12. The term "peptides" in this context may refer to intrinsic factor itself, which is a glycoprotein. Without adequate intrinsic factor, vitamin B12 cannot be properly absorbed in the intestines, leading to the condition. The abbreviation "nan" is not relevant to the context of pernicious anemia.