Megaloblastic (Pernicious) Anemia

February 8, 2017

Megaloblastic anemia is a type of anemia characterized by very large red blood cells. In addition to the cells being large, the inner contents of each cell are not completely developed. This malformation causes the bone marrow to produce fewer cells, and sometimes the cells die earlier than the 120-day life expectancy. Instead of being round or disk-shaped, the red blood cells can be oval.

The term ‘megaloblastic anaemia’ incorporates two different types of anaemia – vitamin B12 deficiency anaemia and folate deficiency anaemia. Most people with either of these conditions will have underdeveloped, larger than normal red blood cells. These do not function properly and will crowd out the healthy cells, which leads to anaemia. Also, because they are underdeveloped, they will have a shorter than normal life expectancy.

Megaloblastic anaemia is typically diagnosed with a blood test and can be treated by a change in diet to feature foods high in vitamin B12 or folic acid (the artificial form of folate).


There are many causes of megaloblastic anemia, but the most common source in children occurs from a vitamin deficiency of folic acid or vitamin B12. Other sources of megaloblastic anemia include the following –

Digestive diseases – Certain diseases of the lower digestive tract can lead to megaloblastic anemia. These include celiac disease, chronic infectious enteritis, and enteroenteric fistulas. Pernicious anemia is a type of megaloblastic anemia caused by an inability to absorb vitamin B12 due to a lack of intrinsic factor in gastric (stomach) secretions. Intrinsic factor enables the absorption of vitamin B12.

Malabsorption – Inherited congenital folate malabsorption, a genetic problem in which infants cannot absorb folic acid in their intestines, can lead to megaloblastic anemia. This requires early intensive treatment to prevent long-term problems, such as intellectual disability.

Medication-induced folic acid deficiency – Certain medications, specifically ones that prevent seizures, such as phenytoin, primidone, and phenobarbital, can impair the absorption of folic acid. The deficiency can usually be treated with a dietary supplement.

Folic acid deficiency – Folic acid is a B vitamin required for the production of normal red blood cells. Folate, the naturally occurring form, is present in foods, such as green vegetables, liver, and yeast. Folic acid is produced synthetically and added to many food items, including breads and cereals.

Risk Factors

In adults, symptoms of pernicious anemia are usually not seen until after age 30. The average age of diagnosis is age 60.

People are more likely to get this disease if they –

  • Are Scandinavian or Northern European
  • Have a family history of the condition

Certain diseases can also raise the risk. They include –

  • Addison disease
  • Chronic thyroiditis
  • Graves disease
  • Hypoparathyroidism
  • Hypopituitarism
  • Myasthenia gravis
  • Secondary amenorrhea
  • Type 1 diabetes
  • Testicular dysfunction
  • Vitiligo


These are some of the symptoms of megaloblastic anemia –

  • Pale or yellow skin
  • Fast heart beat
  • Shortness of breath
  • Lack of energy, feeling tired
  • Decreased appetite
  • Irritability or fussiness
  • Hair color changes
  • Stomach upsets, nausea, diarrhea, gas, constipation
  • Trouble walking
  • Numbness or tingling in hands and feet
  • Smooth and sore tongue
  • Weak muscles

The symptoms of megaloblastic anemia may look like other conditions or medical problems. Always check with your child’s doctor for a diagnosis.


In general, anemia may cause –

  • Problems with growth and development
  • An enlarged heart, heart failure

Megaloblastic anemia can also cause problems with the nervous system.


Vitamin B12 injections are usually given daily for 1 week, then weekly for 4 weeks, and then monthly until hematologic indices have stabilized. Patients with continued risk of deficiency should remain on monthly injections. Oral B12 may be substituted in highly compliant patients. At high intakes, the vitamin enters the body through diffusion. Vitamin B12 sublingual preparations and a nasal gel are also available for maintenance therapy when compliance is ensured.

Folate – Oral folate taken daily for several months usually corrects the deficiency.  Concomitant B12 deficiency must be ruled out, as folate supplementation can mask the hematologic signs of B12 deficiency, leading to irreversible neurological injury if not treated. This masking is more likely to occur in patients routinely prescribed folate for other medical reasons (eg, sickle cell anemia).


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