A 42-year-old man comes to the office due to numbness and tingling in both legs and difficulty walking for the past several months. He has also noticed that he tires more easily with physical activity. Temperature is 36.8 C (98.2 F), blood pressure is 122/86 mm Hg, pulse is 76 /min, and respirations are 14/min. Physical examination shows conjunctival pallor and loss of vibration and position sensation in the bilateral lower extremities with associated gait ataxia. The remainder of the examination is within normal limits. Which of the following findings is most likely to be present on further questioning of the patient?
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This patient most likely has deficiency of vitamin B12 (cobalamin), a water-soluble vitamin obtained solely from the diet, specifically animal products such as meat, dairy, and fish. Vitamin B12 cannot be obtained directly from plant products, placing strict vegans at risk for dietary deficiency, particularly those who do not eat vitamin B12–fortified foods; without supplementation, patients with impaired intrinsic factor production (eg, pernicious anemia, total gastrectomy) also inevitably develop deficiency.
The liver can store approximately 1,000 times the daily vitamin B12 requirement; deficiency develops only after the complete absence of intake or absorption for 3-4 years, making a long-standing (ie, 6 years) vegan diet consistent with this patient's presentation, in contrast to a recent (ie, 8 months) gastrectomy (Choice C).
Development of anemia and severe, potentially irreversible neurologic damage can result from vitamin B12 deficiency. Red blood cell synthesis relies on vitamin B12–dependent recycling of folate; deficiency of either vitamin results in megaloblastic anemia. Impaired myelin synthesis, specifically in the dorsal and lateral columns, results in subacute combined degeneration of the spinal cord. This condition is progressive and begins as a symmetric neuropathy consisting of paresthesia and weakness. Ongoing deficiency leads to loss of vibration and position sensation with development of an ataxic gait. The longer the deficiency is untreated, the less likely the neurologic deficits can be reversed.
(Choice A) Isoniazid is often used to treat latent tuberculosis infection. It impairs the availability of vitamin B6, which can result in peripheral neuropathy in high risk patients (eg, pregnancy, HIV, diabetes mellitus); anemia (eg, conjunctival pallor) would be unexpected.
(Choice D) Phenytoin, an antiepileptic drug used to treat focal and generalized seizures, may result in folate deficiency and development of megaloblastic anemia. Phenytoin can also cause peripheral neuropathy, but this adverse effect usually occurs only with chronic therapy (>1 year).
(Choice E) Vitamin D deficiency can develop over several months due to inadequate dietary intake and minimal sunlight exposure. This deficiency presents as rickets in children and osteomalacia or osteoporosis in adults.
Educational objective:
Vitamin B12 is obtained through the diet solely from animal sources, which places strict vegans at risk for dietary deficiency. This deficiency takes years to develop due to the large hepatic vitamin B12 reserve, and presents with megaloblastic anemia and potentially irreversible neurologic deficits (eg, paresthesia, weakness, ataxic gait).