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Megaloblastic Anemia

Last updated Nov. 17, 2018

Megaloblastic Anemia is a type of anemia (decrease in red blood cell, decrease in hemoglobin in red blood cell, or decrease in blood volume).


What are the other Names for this Condition? (Also known as/Synonyms)

  • Megaloblastic Anaemia
  • Rogers Syndrome

What is Megaloblastic Anemia? (Definition/Background Information)

  • Megaloblastic Anemia is a type of anemia (decrease in red blood cell, decrease in hemoglobin in red blood cell, or decrease in blood volume). It develops as a response by the body to deficiency in either vitamin B12 (cobalamin) or folate. Both are essential vitamins required for DNA production in the cells
  • Anemia develops when red blood cells (RBCs) lack sufficient vitamin B12 and/or folate to fully mature. The condition is called Megaloblastic Anemia because the RBCs appear very big on a microscopic examination
  • The depletion of vitamin B12 from body stores is a slow process that may take many years; although, folate may be depleted within a few weeks
  • All actively dividing (proliferating) cells in the body can be affected in Megaloblastic Anemia, and not just the red blood cells
  • Anemia causes weakness, fatigue, loss of appetite, weight loss, and even skin color changes. Severe anemia can also cause heart failure, if it is long-standing
  • Administration of the deficient vitamin B12 or folate is the first line of treatment for Megaloblastic Anemia, though severe cases may require blood transfusions. If no complications develop, the prognosis of the condition is generally good with suitable treatment

Who gets Megaloblastic Anemia? (Age and Sex Distribution)

  • Megaloblastic Anemia can occur in any individual of any age, since it is caused by insufficient dietary intake of vitamin B12 (cobalamin) or folate. The condition is commonly seen in elderly adults, especially due to folate deficiency or pernicious anemia (a type of vitamin B12 deficient anemia)
  • Though both males and females are affected, it is more commonly observed in females during pregnancy due to folate deficiency
  • Megaloblastic Anemia can be seen in any part of the world; however, it is more common in countries (regions) where malnutrition is common, such as Africa, India, parts of Asia, and South America
  • Pernicious anemia is more common in Scandinavian countries and among Caucasians

What are the Risk Factors for Megaloblastic Anemia? (Predisposing Factors)

Factors that increase the risk for developing vitamin B12 or folate deficiency include:

  • Elderly age and infancy (especially premature babies)
  • Gastric bypass surgery and gastrectomy
  • A diet lacking foods that contain adequate quantities of
    • Vitamin B12 such as meat, whole grains, fish, dairy, and eggs
    • Folate such as leafy green vegetables (like spinach), nuts, yeast, and liver             
  • Alcoholism and chronic pancreatitis (causing impaired absorption of vitamin B12)
  • Anatomic abnormalities of the intestines that allow bacterial overgrowth
  • Infection with HIV
  • Cancer and inflammatory diseases
  • Myelodysplastic syndromes
  • Use of medications for epilepsy, HIV infection, cancer, and autoimmune diseases

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Megaloblastic Anemia? (Etiology)

Megaloblastic Anemia can be caused by B12 deficiency, folate deficiency, or mechanisms independent of the two nutrients.

  • Causes of vitamin B12 deficiency may include:
    • Insufficient dietary intake of vitamin B12, especially observed in individuals who practice strict vegetarianism
    • Intestinal fish tapeworm infection
    • Gastrointestinal malabsorption syndromes
    • Pernicious anemia (an autoimmune disease leading to intrinsic factor deficiency)
    • Gastric bypass surgery and gastrectomy           
    • Depletion by intestinal bacteria or parasites
  • Causes of folate deficiency may include:
    • Insufficient dietary intake of folate
    • Chronic alcohol abuse
    • Use of anti-folate drugs (e.g. methotrexate), or drugs that interfere with DNA synthesis (e.g. hydroxyurea, 6-mercaptopurine, AZT), and other such drugs
    • Increased need for folate in pregnancy
    • Patients on long-term dialysis             
    • Severe or chronic hemolytic anemia such as sickle cell disease
  • Megaloblastic Anemia less commonly develops when DNA synthesis is inhibited by mechanisms unrelated to vitamin B12 and folate deficiency, such as HIV infections, MDS (myelodysplastic syndromes), and use of certain medications

What are the Signs and Symptoms of Megaloblastic Anemia?

The main function of RBCs is to pick up oxygen in the lungs, to deliver to various body tissues. Vitamin B12 and folate deficiency delay the maturation of newly formed RBCs. A decrease in the number of functional RBCs, leads to decreased oxygen availability to the tissues and thus to the symptoms of anemia. Individuals with mild anemia may have no symptoms; the condition may be incidentally diagnosed following a routine blood test, performed for another health indication.

The signs and symptoms that are generally observed with Megaloblastic Anemia due to deficient cobalamin (vitamin B12) and folate levels may include:

  • Weakness and fatigue
  • Pale mucous membranes
  • Loss of appetite, weight loss
  • Sore tongue, inflammation of the tongue (glossitis)
  • Diarrhea or constipation
  • Cracking and inflammation at the corners of the mouth (angular cheilitis)
  • Skin color changes

Symptoms associated with Megaloblastic Anemia due to B12 deficiency:

  • Nerve-related (neurologic) abnormalities is specific to B12 deficiency
  • Parasthesias (tingling and numbness of skin)
  • Difficulty with balance and proprioception (related to coordination of various body parts)
  • Muscle weakness
  • Dementia and psychiatric abnormalities

How is Megaloblastic Anemia Diagnosed?

The diagnosis of Megaloblastic Anemia may involve the following exams and tests:

  • Thorough evaluation of the individual’s medical history and a complete physical examination. An evaluation of medical history including diet history will determine if there is a presence of predisposing factors, such as history of surgery, associated disorders, alcohol intake, etc. Physical examination and clinical workup may uncover findings such as pale tongue, conjunctiva, numbness, heart murmur, and other symptoms
  • Megaloblastic Anemia is diagnosed by performing blood tests that include:
    • Serum B12 level
    • Serum methylmalonic acid level
    • Serum folate level or RBC folate level
    • Complete blood count
    • Peripheral blood smear that demonstrates megaloblastic red blood cells          
  • Occasionally, a bone marrow biopsy is necessary to rule-out or confirm other causes that can mimic Megaloblastic Anemia
  • Special tests may be undertaken, if an autoimmune disease (pernicious anemia) is suspected as the cause. Patients may have antibodies (intrinsic factor), which prevent the absorption of vitamin B12 that can be detected by a blood test
  • Urine tests may be performed to measure the ability of the body to absorb vitamin B12, to help determine the cause of Megaloblastic Anemia

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Megaloblastic Anemia?

The possible complications of Megaloblastic Anemia could include:

  • In severe cases, patients may have decreased numbers of leukocytes (white blood cells) and platelets in blood. This can result in infections, easy bruising, and bleeding
  • Those who are severely deficient in vitamin B12, can also develop bilateral peripheral neuropathy or spinal cord degeneration, causing numbness and muscle weakness in the arms and legs, and difficulty walking
  • Psychiatric symptoms and dementia may be present with severe vitamin B12 deficiency
  • Individuals with pernicious anemia (due to B12 deficiency) are at risk of gastric cancer
  • Infants deficient in vitamin B12 may have poor brain development
  • Folate deficiency during pregnancy increases the risk for serious birth defects (neural tube defects)
  • Congestive heart failure

How is Megaloblastic Anemia Treated?

A treatment of Megaloblastic Anemia may involve the following factors depending on the cause:

  • Once the deficient vitamin is determined, patients are treated with regular injections of the corresponding vitamin B12 (cobalamin) and oral folic acid. Generally, most treated patients begin to feel better within a few doses
  • Severe cases of anemia may be treated with blood transfusion
  • By bringing about changes in one’s dietary habits
  • Treatment of the underlying cause of Megaloblastic Anemia such as autoimmune disease, infection, etc.

How can Megaloblastic Anemia be Prevented?

Certain preventive measures recommended for Megaloblastic Anemia include:

  • Consumption of a healthy diet which includes both plant and animal products
  • Folic acid supplements should be taken by all pregnant women to help prevent folate deficiency, due to increased requirement during the pregnancy period
  • Strict vegetarians/vegans should discuss with their healthcare providers, about how they could incorporate vitamin B12 into their diet

What is the Prognosis of Megaloblastic Anemia? (Outcomes/Resolutions)

  • Megaloblastic Anemia is usually treatable in a matter of weeks and does not affect life expectancy
  • However, the treatment should be started as soon as possible, in order to help prevent any adverse complications
  • The prognosis of Megaloblastic Anemia not arising from deficient folate and cobalamin levels, depends on the underlying cause

Additional and Relevant Useful Information for Megaloblastic Anemia:

During pregnancy, folate supplements help prevent neural tube defects and cleft palate in the developing child. Folic acid during pregnancy has also shown to decrease the incidence of one form of childhood leukemia. Supplements should be started prior to conception, in order for it to be most effective.

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 31, 2015
Last updated: Nov. 17, 2018