1. Be aware of the limitations of laboratory tests.Signs and symptoms of vitamin B12 deficiency can arise even when serum levels are borderline or in the low-normal range. There are several reasons for this. Current assays measure the total amount of B12 on two carrier proteins, haptocorrin and transcobalamin. However, only transcobalamin actively delivers B12 to tissues. In addition, current assays can give false normal results if the patient has a high titre of anti-intrinsic factor antibodies.1 If you have a high clinical index of suspicion of deficiency consider additional tests, such as holo-transcobalamin and metabolic markers of deficiency such as serum homocysteine and methylmalonic acid. You may have to discuss the availability of these with your local laboratory.
2. Vitamin B12 deficiency can exist in the absence of macrocytic anaemia.It is important to remember that vitamin B12 deficiency is not synonymous with pernicious anaemia (PA). Autoimmune PA is just one cause of B12 deficiency. Low levels of B12 can exist in the absence of macrocytic anaemia. In fact, the neuropsychiatric and haematological features of deficiency are frequently dissociated. 2
3. Vitamin B12 deficiency can cause behavioural changesPatients often complain of ‘waking up tired’ even after a good night’s sleep. They may also complain of a lack of mental clarity, nominal aphasia, short-term memory loss and repetition. Irritability, frustration and impatience with a desire for isolation and an aversion to bright lights are also common. All these can have an adverse impact on family life and workplace performance leading to anxiety and depression.
4. The anaemia of B12 deficiency can present in various waysBreathlessness can manifest as panting during physical exertion or regular deep breaths. It can also present as continual sighing or yawning. The low red blood cell count may lead to an increased flow state perceived as pulsatile tinnitus. Patients may complain of ‘screaming’, ‘whistling’ ‘screeching’ or other strange sounds.
5. Remember that the gastrointestinal tract may be involvedSudden and unaccountable bouts of diarrhoea are common. The tongue may appear swollen/beefy and smooth or red with cracks and will be larger than usual. This usually resolves rapidly with vitamin B12 replacement.
6. B12 deficiency produces many neurological signs and symptomsNeurological signs usually generate a clinical picture of combined sclerosis of the spinal cord, but can vary across a wide clinical spectrum. Left undiagnosed and untreated, vitamin B12 deficiency leads to paraesthesia, numbness, gait disturbance, balance and coordination problems, and vertigo. Patients may experience burning legs and/or feet (Grierson-Gopalan syndrome) affecting one or both limbs, typically worse in the evenings. All patients with neurological symptoms should also be referred to a haematologist.
7. Check for concomitant medications that might interfere with vitamin B12 absorptionMedications that reduce stomach acid, such as H2-receptor antagonists or PPIs, may reduce vitamin B12 absorption from food and these patients might benefit from supplementation. Metformin, slow-release potassium supplements, colchicine and AZT can also reduce absorption of vitamin B12 and may contribute to deficiency. Although serum concentrations of B12 may be lowered by oral contraceptives, a recent study found no metabolic evidence of deficiency in such patients.
8. Remember the at-risk groupsVitamin B12 deficiency is common in the elderly, but can occur at all stages of life including infancy. Additional risks are:
- Previous gastric and bowel surgery, which may reduce absorption.
- Other autoimmune diseases, which often co-exist with vitamin B12 deficiency, such as diabetes, thyroiditis, and psoriasis.
- Strict vegetarianism: up to 88% of vegans who do not take supplements can be deficient.
- Dietary intolerance: it is also important to be aware that bioavailability of vitamin B12 may be low in goat’s milk.