Vitamin B12 Deficiency

Vitamin B12 deficiency, also known as cobalamin deficiency, is a condition where the blood and tissues have lower than normal levels of vitamin B12. This deficiency can lead to a variety of symptoms and complications, affecting numerous bodily systems, including neurological and haematological functions.

Signs, Symptoms, and Complications

Vitamin B12 deficiency manifests with a wide range of symptoms, which can vary in severity. Mild deficiency might present with few or no symptoms, whereas moderate deficiency can cause fatigue, headaches, mouth ulcers, breathlessness, rapid heartbeat, and cognitive impairments. Severe deficiency may lead to more serious neurological symptoms such as impaired reflexes, muscle weakness, memory problems, depression, anxiety, and psychosis. In infants, it can cause poor growth and developmental issues.

Possible oral manifestation of B12 deficiency: erythema and depapillation of the tongue in a patient. From Kim et al., 2016.

Severe deficiency can lead to a neurological condition known as subacute combined degeneration of the spinal cord, characterised by impaired perception of touch, ataxia, diminished reflexes, and severe paresis. Additionally, vitamin B12 deficiency may result in megaloblastic anaemia, a condition where red blood cells are larger than normal and ineffective in oxygen transport.

Causes

The primary causes of vitamin B12 deficiency include poor absorption, inadequate dietary intake, and increased bodily requirements. Poor absorption is often related to pernicious anaemia, where autoantibodies attack stomach cells responsible for producing intrinsic factor, essential for B12 absorption. Other causes include gastrointestinal surgeries, chronic inflammation, certain medications, and genetic disorders. Inadequate dietary intake is more common among vegetarians and vegans, while increased needs can occur in conditions like HIV/AIDS.

Diagnosis

Diagnosis of vitamin B12 deficiency is typically based on blood tests showing levels below 148–185 pmol/L (200–250 pg/mL). Elevated levels of methylmalonic acid (MMA) can also indicate deficiency. The presence of antibodies to gastric parietal cells and intrinsic factor may suggest pernicious anaemia. Additionally, neurological symptoms can precede haematological signs, and a complete blood count may show anaemia with elevated mean cell volume.

MRI image of the brain in vitamin B12 deficiency, axial view showing the "precontrast FLAIR image": note the abnormal lesions (circled) in the periventricular area suggesting white matter pathology.

Treatment

Treatment for vitamin B12 deficiency involves supplementation, either orally or via injection. Initially, high daily doses are given, followed by less frequent, lower doses as the condition improves. Lifelong B12 administration is often recommended if no reversible cause is found. In severe cases, injections are preferred over oral supplements. It is important to address any underlying causes of the deficiency if possible. Additionally, folic acid supplementation should be avoided in untreated B12 deficiency as it can mask anaemia without addressing neurological damage.

Hydroxocobalamin injection is a clear red liquid solution.

Epidemiology

Vitamin B12 deficiency is common worldwide. In the UK and US, around 6% of the general population is affected, with the prevalence increasing to 20% in those over 60. In some developing regions, the deficiency rate can be as high as 70-80%. The World Health Organisation considers vitamin B12 deficiency a global public health issue, although accurate global prevalence data is limited.

Image of the cervical spinal cord in vitamin B12 deficiency showing subacute combined degeneration. (A) The midsagittal T2 weighted image shows linear hyperintensity in the posterior portion of the cervical tract of the spinal cord (black arrows). (B) Axial T2 weighted images reveal the selective involvement of the posterior columns.

History

The understanding of vitamin B12 deficiency has evolved significantly since the 19th century. Early descriptions of pernicious anaemia by Thomas Addison and others laid the groundwork for later discoveries. In the 1920s, George Whipple and colleagues demonstrated that liver consumption could treat the condition, leading to the identification of vitamin B12 as the very important factor. This discovery earned Whipple, Minot, and Murphy the Nobel Prize in Physiology or Medicine in 1934.

Self-assessment MCQs (single best answer)

Which of the following is NOT a symptom of mild vitamin B12 deficiency?

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What is the characteristic neurological condition associated with severe vitamin B12 deficiency?

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Which of the following is a primary cause of vitamin B12 deficiency?

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What diagnostic marker, besides low B12 levels, can indicate vitamin B12 deficiency?

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Which group is more likely to have inadequate dietary intake of vitamin B12?

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What is the recommended treatment for severe cases of vitamin B12 deficiency?

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Which of the following is a common haematological finding in vitamin B12 deficiency?

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What landmark discovery in the 1920s helped treat pernicious anaemia?

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Which diagnostic test can confirm pernicious anaemia as a cause of vitamin B12 deficiency?

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What is the prevalence of vitamin B12 deficiency in people over the age of 60 in the UK and US?

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