Vitamin B12 deficiency: Clinical sciences

Vitamin B12 deficiency occurs when the body lacks sufficient vitamin B12, which is crucial for adequate DNA synthesis, nerve myelination, and fatty acid oxidation. Vitamin B12, also known as cobalamin, is found in animal products like meat, eggs, dairy, and fortified cereals. So, inadequate intake of these foods, malabsorptive conditions, and some medications, can lead to vitamin B12 deficiency. The diagnosis is primarily made based on vitamin B12 levels, complete blood count, and peripheral blood smear.

Now, when a patient presents with a chief concern suggesting vitamin B12 deficiency, the first step is to perform a focused history and physical examination. The patient may report fatigue, palpitations, numbness, and tingling in their extremities. In severe cases, they may also report impaired gait or falls; as well as neuropsychiatric symptoms, such as cognitive impairment or mood changes. Additionally, your patient might present with risk factors for vitamin B12 deficiency. These include inadequate dietary intake, seen in strict vegetarians or vegan diets, and conditions that decrease B12 absorption, like gastric bypass surgery or inflammatory bowel disease; as well as medications that interfere with B12 metabolism, such as metformin, or medications that interfere with B12 absorption, like proton pump inhibitors.

Additionally, the physical exam may reveal glossitis, often described as berry red patches on the lingual surface. In severe cases, vitamin B12 deficiency can lead to subacute combined degeneration, an advanced form of central nervous system neuropathy associated with demyelination of the dorsal and lateral columns of the spinal cord. Important findings in these individuals include sensory ataxia, as well as loss of proprioception, impaired vibratory sensation, and in some cases, progressive muscle weakness. At this point, you should suspect vitamin B12 deficiency.

Now, here’s a clinical pearl! Nitrous oxide, used either as an anesthetic agent or as a recreational drug, can cause functional B12 deficiency by forcing the metabolic conversion of vitamin B12 into its inactive form. This can lead to acute, severe neurologic symptoms, especially in patients with underlying B12 deficiency!

Now, once you suspect Vitamin B12 deficiency, your next step is to order labs, including a vitamin B12 level, CBC, and peripheral smear. If your patient’s B12 level, CBC, and peripheral smear are all normal, consider an alternative diagnosis.

Now, let’s move on to patients that present with vitamin B12 levels on the low end of normal. Although this number is technically in the normal range, the fact that it’s on the lower end should make you want to check the CBC and peripheral smear. In fact, your patient could have low hemoglobin, high MCV, and megaloblastic anemia, which is characterized by macrocytic red blood cells and hypersegmented neutrophils on peripheral smear. What’s important here is that megaloblastic anemia indicates that there's a clinically significant B12 deficiency.

In this case, you should check the patient’s methylmalonic acid, and consider checking homocysteine levels, which are two substrates that use B12 as a cofactor for enzymatic conversion. So, if methylmalonic acid and homocysteine levels are normal, then consider an alternative diagnosis. On the other hand, if vitamin B12 is deficient, these enzymatic conversions cannot occur, so both methylmalonic acid and homocysteine will be elevated. If this is the case, diagnose vitamin B12 deficiency!

Here’s a clinical pearl! Folate deficiency can present similarly to B12 deficiency. Both cause megaloblastic anemia with hypersegmented neutrophils, and elevated homocysteine levels. But unlike in B12 deficiency, the methylmalonic acid level in folate deficiency will be normal.

Let’s go back once more to the Vitamin B12 level, CBC, and peripheral smear. If the Vitamin B12 level is low, and the CBC and peripheral smear reveal megaloblastic anemia, then diagnose Vitamin B12 deficiency.

Once you diagnose vitamin B12 deficiency, the next step is to assess the need for intramuscular supplementation. Indications include the presence of severe anemia; severe neurologic manifestations, like cognitive impairment or subacute combined degeneration deficiency; and B12 deficiency due to malabsorption.