ANSWER 18
This patient has a severe macrocytic anaemia and neurological signs due to vitamin B 12 defi-
ciency. There is a family history of thyroid disease. This can cause a macrocytic anaemia but
not to this degree, and hypothyroidism would not explain the other features. Anaemia reduces
tissue oxygenation and therefore can affect most organ systems. The symptoms and signs of
anaemia depend on its rapidity of onset. Chronic anaemia causes fatigue and pallor of the
mucous membranes. Cardiorespiratory symptoms and signs include breathlessness, chest pain,
claudication, tachycardia, oedema and other signs of cardiac failure. Gastrointestinal symp-
toms include anorexia, weight loss, nausea and constipation. There may be menstrual irregu-
larities and loss of libido. Neurological symptoms include headache, dizziness and cramps.
There may be a low-grade fever. In pernicious anaemia, the MCV can rise to 100–140 fL, and
oval macrocytes are seen on the blood film. The reticulocyte count is inappropriately low for
the degree of anaemia. The white cell count is usually moderately reduced. There is often a
mild rise in serum bilirubin giving the patient a ‘lemon-yellow’ complexion. As in this patient,
profound vitamin B 12 deficiency also causes a peripheral neuropathy and subacute degenera-
tion of the posterior columns and pyramidal tracts in the spinal cord, causing a sensory loss
and increased difficulty walking. The peripheral neuropathy and pyramidal tract involvement
produce the combination of absent ankle jerks and upgoing plantars. In its most extreme form
it can lead to paraplegia, optic atrophy and dementia. Vitamin B 12 is synthesized by micro-
organisms and is obtained by ingesting animal or vegetable products contaminated by bacte-
ria. After ingestion, it is bound by intrinsic factor, synthesized by gastric parietal cells, and this
complex is then absorbed in the terminal ileum. Vitamin B 12 deficiency is most commonly of
a gastric cause (pernicious anaemia due to an autoimmune atrophic gastritis; total gastrec-
tomy), bacterial overgrowth in the small intestine destroying intrinsic factor, or a malabsorp-
tion from the terminal ileum (surgical resection; Crohn’s disease).
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- Folate deficiency
- Excessive alcohol consumption
- Hypothyroidism
- Certain drugs, e.g. azathioprine, methotrexate
- Primary acquired sideroblastic anaemia and myelodysplastic syndromes
Differential diagnoses of macrocytic anaemia- Vitamin B 12 deficiency may occur in strict vegetarians who eat no dairy produce.
- Typical neurological signs are position and vibration sense impairment in the legs,
absent reflexes and extensor plantars. - Overenthusiastic blood transfusion should be avoided since it can provoke cardiac
failure in vitamin B 12 deficiency.
KEY POINTS
A full dietary history should be taken. Vegans who omit all animal products from their diet
often have subclinical vitamin B 12 deficiency. Serum vitamin B 12 and folate levels should
be measured and antibodies to intrinsic factor and parietal cells should be assayed. Intrinsic
factor antibodies are virtually specific for pernicious anaemia but are only present in about
50 per cent of cases. Parietal cell antibody is present in 85–90 per cent of patients with per-
nicious anaemia but can also occur in patients with other causes of atrophic gastritis.
A radioactive B 12 absorption test (Schilling test) distinguishes gastric from intestinal causes
of deficiency. Rapid correction of vitamin B 12 is essential using intramuscular hydroxy-
cobalamin to prevent cardiac failure and further neurological damage.