Maude McArthur, a 75 year old widow from the nearby retirement village presents complaining of a sore tongue. It has become quite difficult to eat lately and she is really only having tea and toast. You observe that Maude's tongue is quite inflamed as well as the corners of her mouth.
You are concerned about Maude's diet and think she may have a nutritional problem.
You suspect a nutritional deficiency in B12 and folate, so on history and examination you would need to enquire about:
Folate is present in most foods, notably green vegetables, liver and nuts, but it may be destroyed by cooking. In patients with grossly deficient diets folate deficiency is relatively common because stores are meagre, being sufficient for only 3-4 months.
Examination:
A full haematological examination should be completed. In particular look for signs of severe anaemia, including pallor, tachycardia, wide pulse pressure, systolic ejection murmurs due to a compensatory rise in cardiac output, and cardiac failure if myocardial reserve is reduced.
The legs should also be examined for evidence of the neurological abnormalities caused by vitamin B12 deficiency: peripherally neuropathy, and subacute combined degeneration of the spinal cord. B12 deficiency can also result in optic atrophy, and mental changes.
Clinical signs of folate and B12 deficiency:
Skin
Gut
CNS
Eyes
Vitamin B12 and folate are important for DNA synthesis in red cell metabolism.
The human body needs folate and vitamin B 12 to synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in biological reactions involving folate. It is especially important during periods of rapid cell division and growth.
B12 and folic acid are coenzymes in the DNA synthetic pathway. A deficiency of these vitamins or impairment in their utilization results in deranged or inadequate synthesis of DNA. The synthesis of RNA and protein is unaffected, however, so there is cytoplasmic enlargement not matched by DNA synthesis, which appears to delay or block mitotic division. Thus there appears to be asynchronism between the cytoplasmic maturation and nuclear maturation.
Vitamin B12, or cyanocobalamin, is a group of cobalt-containing water-soluble vitamins. They are coenzymes necessary for red blood cell production - folate polyglutamate is the major red cell form of folate. Vitamin B12 is derived primarily from food of animal origin, including dairy products. Absorption of B12 from the gastrointestinal tract is dependent on acid and intrinsic factor secreted by the gastric mucosa. The recommended daily average intake in the adult is 3-5 micrograms. A normal liver stores about 3 mg which is sufficient for several years.
Pernicious anaemia (PA) is a disease of the stomach that is characterised by megaloblastic anaemia due to vitamin B12 deficiency, itself, secondary to intrinsic factor deficiency and gastric atrophy. It usually has an autoimmune basis.
PA primarily affects the elderly - most patients are over 60 years of age; less than 10% of cases are under 40 years of age; it is rare in children. Women are affected more often than men, in a ratio of 3:2.
Auto-antibodies to gastric parietal cells are present in 90% of cases but are not pathognomonic as they may occur:
Auto-antibodies to intrinsic factor are more specific. They are found in the serum in 55% of cases and in gastric juice in 80%. They are of two types:
Anti – intrinsic factor antibodies are widely available for testing of PA. They have a sensitivity of 50 – 60 % and a specificity approaching 100% for the diagnosis. Antiparietal cell antibodies are more sensitive but less specific.
Gastric biopsy may demonstrate chronic atrophic gastritis, and due to the increased risk of gastric malignancy, referral to a gastroenterologist for gastric monitoring is usually indicated.
The Schilling test is the classic test for inadequate B12 absorption and consists of two parts. The first part remains available in a number of laboratories; the second part is no longer performed because of the unavailability of intrinsic factor. The test is rarely of additional clinical utility.