A 63-year-old woman goes to her general practitioner (GP) complaining of extreme tiredness.
She has been increasingly fatigued over the past year but in recent weeks she has
become breathless on exertion, light-headed and complained of headaches. Her feet have
become numb and she has started to become unsteady on her feet. She has had no significant
previous medical illnesses. She is a retired teacher and lives alone. Until the last
2 years she was active, walking 3 or 4 miles a day. She is a non-smoker and drinks about
15 units of alcohol per week. She is taking no regular medication. Her mother and one of
her two sisters have thyroid problems.
Examination
Her conjunctivae are pale and sclerae are yellow. Her temperature is 37.8°C. Her pulse rate
is 96/min regular, and blood pressure 142/72 mmHg. Examination of her cardiovascular,
respiratory and abdominal systems is normal. She has a symmetrical distal weakness
affecting her arms and legs. Knee and ankle jerks are absent and she has extensor plantar
responses. She has sensory loss in a glove and stocking distribution with a particularly
severe loss of joint position sense.
ANSWER
This patient has a severe macrocytic anaemia and neurological signs due to vitamin B12 deficiency.
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 symptoms
include anorexia, weight loss, nausea and constipation. There may be menstrual irregularities
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 100–140fL, 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 B12 deficiency also causes a peripheral neuropathy and subacute degeneration
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 B12 is synthesized by microorganisms
and is obtained by ingesting animal or vegetable products contaminated by bacteria.
After ingestion, it is bound by intrinsic factor, synthesized by gastric parietal cells, and this
complex is then absorbed in the terminal ileum. Vitamin B12 deficiency is most commonly of
a gastric cause (pernicious anaemia due to an autoimmune atrophic gastritis; total gastrectomy),
bacterial overgrowth in the small intestine destroying intrinsic factor, or a malabsorption
from the terminal ileum (surgical resection; Crohn’s disease).