Megaloblastic Anaemia (Vitamin B12 and Folate)

Anaemia is the medical term for a deficiency of hemoglobin, the compound in the red blood cells that bind to oxygen. It may be related to low numbers of red blood cells or lower than normal levels of haemoglobin although there is sufficient red blood cells. There are various types of anemia associated with normal or abnormal red blood cells. One of these is megaloblastic anaemia. It arises when there is a deficiency of vitamin B12 and folate (vitamin B9).

Abnormally Large Red Blood Cells

Red blood cells are about 7 micrometers in diameter and disc-shaped. All the red blood cells are the same size and shape. This size and shape ensures that red blood cell can move freely in the blood and squeeze through even the tiniest of blood vessels in the body. However in megaloblastic anaemia, the red blood cells are too large and the shape may be distorted. The red blood cells are also more fragile than normal and is easily ruptured. Others die within the bone marrow where it is produced or for some unknown reason just ruptures on its own. Collectively this leads to lower levels of red blood cells.

Causes of Megaloblastic Anemia

It is important to first understand more about the life cycle of red blood cells. These cells are produced in the bone marrow from haematopoietic stem cells. It undergoes several stages of development during a period of 7 days to emerge as a mature red blood cell in the bloodstream. During its maturation, it requires vitamin B12 and folate for the synthesis of DNA, the genetic blueprint that is present in every cell in the body. Without the proper blueprint, the characteristics of individual cells are affected.

Most of the causes of megaloblastic anemia relate to either a low intake of vitamin B12 and folate or decreased absorption of these nutrients from the gut. Starvation, excessive and strict dieting and fasting, and vegetarianism especially in fussy eaters may lead to a deficiency of vitamin B12 and folate. However the more common cause is related to malabsorption. This may be seen with a range of stomach and bowel diseases. The stomach produces an important compound known as intrinsic factor which is necessary for vitamin B12 absorption. Since the small intestine is the site of nutrient absorption, if it is diseased the absorption of macro- and micronutrients will be affected. Some bowel diseases where vitamin B12 and folate deficiency occurs includes Crohn’s disease (inflammatory bowel disease), chronic enteritis, scleroderma, Whipple disease, tropical sprue and intestinal lymphoma.

Other causes may include increased utilisation of these micronutrients like in pregnancy where the demands of the foetus drains the mother’s resources. A number of drugs are also reported to cause a deficiency and includes medication like methotrexate, oral contraceptives, anti-epileptic drugs, anti-gout medication and certain antibiotics. In conditions like HIV and certain disease like leukaemia, the synthesis of DNA is disrupted despite there being sufficient folate and vitamin B12.

Signs and Symptoms

Megaloblastic anaemia develops very slowly so patients will be without symptoms (asymptomatic) for long periods of time. Gradually non-specific symptoms like breathlessness, fatigue and a feeling of being unwell (malaise), mouth pain without any sores, abnormal sensations on the skin, weight loss and fever will set in.

Other more specific signs and symptoms include grey hair, pale yellow skin, vitiligo, cracking of the corner of the mouth and a smooth tongue. Patients will also complain of a poor memory, depression, personality changes and a loss of libido. Eventually heart failure may set in.

Read more on vitamin B12 deficiency and folate deficiency for information on treatment.