(Vitamin B12 or Folate Deficiency)

Megaloblastic anemia is a form of anemia characterized by very large red blood cells and a decrease in the number of those cells. Anemias are blood disorders that occur when the body has fewer red blood cells than normal. Red blood cells carry oxygen throughout the body using a protein called hemoglobin. If there aren’t enough of these cells or this protein, anemia results.

Usually, megaloblastic anemia is due to acquired deficiency in vitamin B12 or folic acid. The deficiency can be related to inadequate dietary intake of these B vitamins or poor intestinal absorption. Rarely, megaloblastic anemias are the result of medications or inherited defects in the transport/metabolism of vitamin B12 or folic acid.

Pernicious anemia is a type of megaloblastic anemia in which the body isn’t able to absorb vitamin B12 due to a lack of intrinsic factor in stomach secretions. Intrinsic factor is needed for the body to absorb vitamin B12.

For all types of megaloblastic anemia, in addition to the red blood 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 red blood cells die earlier than the 120-day life expectancy.

Megaloblastic Anemia Treatment

Children and young adults with megaloblastic anemia are treated through the Blood Disorders Center.

What are megaloblastic anemia symptoms?

Each child may experience symptoms of pernicious anemia differently. Some children with pernicious anemia do not have symptoms, or they may be mild. Common symptoms of the condition include:

• pale skin, lips and hands
• decreased appetite
• irritability
• lack of energy or fatigue
• diarrhea or constipation
• difficulty walking (Vitamin B12 specific)
• numbness or tingling in hands and feet (Vitamin B12 specific)
• smooth and tender tongue
• weak muscles (Vitamin B12 specific)
• Lightheadedness upon standing or exertion
• Difficulty concentrating
• Shortness of breath (primarily during exercise)
• Swollen, red tongue
• Bleeding gums

It is important to understand that some symptoms of megaloblastic anemia may resemble those of other more common medical problems or other blood disorders. Because some of these symptoms can also point to other conditions, and because anemia itself can be a symptom of another medical problem, it’s important to have your child evaluated by a qualified medical professional for an accurate diagnosis and prompt treatment.

What are the causes of megaloblastic anemia?

Megaloblastic anemia most commonly results from an acquired nutritional deficiency or inability to absorb nutrients. Common causes include:

• dietary deficiency of folic acid. Folic acid is a “B” vitamin required for the production of normal red blood cells. Folic acid is present in foods such as green vegetables, liver, and yeast. It is also produced synthetically and added to many food items.
• dietary deficiency of vitamin B12. Vitamin B12, which the body needs to make red blood cells and to keep the nervous system working properly, is found primarily in meat and foods of animal origin. Strict vegans who do not take vitamin B12 supplements may have vitamin B12 deficiency.
• certain diseases of the lower digestive tract, including celiac disease, chronic infectious enteritis, and enteroenteric fistulas.
• a weakened stomach lining, called atrophic gastritis.
• an autoimmune attack on the stomach cells that produce intrinsic factor, the binding partner of Vitamin B12 that allows it to be absorbed further down the intestine. Pernicious anemia, a type of megaloblastic anemia, occurs when the stomach doesn’t make enough intrinsic factor, so the intestines cannot absorb B12 properly.
• 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.

In rare cases, megaloblastic anemia is the result of inherited problems:

• Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare inherited megaloblastic anemia characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus.
• Congenital (inherited) vitamin B12 deficiency can be the result of inherited deficiency of intrinsic factor or the receptor in the intestines (Imerslund-Grasbeck syndrome), or other vitamin B12 transporters (Transcobalamin deficiency).
• Inherited congenital folate malabsorption is a genetic problem in which infants cannot absorb folic acid in their intestines. This requires early intensive treatment to prevent long-term problems, including significant intellectual disabilities.

How is megaloblastic anemia diagnosed?

Your child’s doctor may suspect megaloblastic anemia after taking a complete medical history and physical examination of your child. Megaloblastic anemia is diagnosed through a physical exam and other tests, including:

• complete blood count
• reticulocyte count, which measures how fast premature red blood cells, called reticulocytes, are made by bone marrow and released into blood
• blood tests to measure of vitamin B12, methylmalonic acid (MMA) or homocysteine levels
• blood tests to detect the antibodies toward intrinsic factor or the cells that produce it
• a bone marrow exam may be necessary if the diagnosis is unclear.

There may be other diagnostic tests that your doctor will discuss with you depending on your child’s individual situation. After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child’s condition. Then we will meet with you and your family to discuss the results and outline the best possible treatment options.

What are the treatments for megaloblastic anemia?

Megaloblastic anemia treatment typically includes:

• replacing any nutritional deficiencies through:
• changes in diet to include foods that are rich in folic acid and vitamin B12, such meat and liver, green, leafy vegetables, citrus fruits, and berries.
• taking an oral dietary folic acid supplement for at least two to three months.
• injections of vitamin B12 once a month (or more if your child has severely low levels of vitamin B12), vitamin B12 supplements by mouth, or a combination.
• addressing the absorption problem in the digestive tract, if that is what is causing the condition.

Of course, your child’s team of doctors will help determine the best approach for your child’s unique situation, based on a number of factors including:

• The underlying cause of the megaloblastic anemia
• Your child’s age, overall health and medical history
• The severity of the disease
• Your child’s tolerance for certain medications, procedures or therapies.
• How your child’s doctors expect the disease to progress
• Your opinion and preferences

What is the latest research on megaloblastic anemia?

Our physician scientists are conducting innovative research on anemias and red blood cell disorders. We have a long track record of innovation, and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is considered a world leader in laboratory and clinical research on blood disorders. Our researchers were the first to clone the gene responsible for thiamine-responsive megaloblastic anemia (TRMA), a type of congenital megaloblastic anemia.

What is the long-term outlook for megaloblastic anemia?

Children with acquired megaloblastic anemia typically do well with treatment. It’s important to start treatment early, especially in vitamin B12 deficiency, as nerve damage can become permanent if treatment does not begin within six months of the onset of symptoms. With ongoing care and proper treatment, most children with acquired megaloblastic anemia recover fully. Outcomes for congenital (inherited) forms of megaloblastic anemia depend on the exact diagnosis.