Methotrexate (an older cancer treatment medication) can be used as first-line therapy for rheumatologic and psoriatic diseases. One of the side effects of methotrexate usage mimics which one of the following vitamin deficiencies?
**Core Concept**
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase (DHFR), an enzyme crucial for the synthesis of tetrahydrofolate (THF). THF is essential for the production of purines and pyrimidines, which are vital components of DNA and RNA. The inhibition of DHFR by methotrexate leads to a decrease in the levels of THF, causing a deficiency in the synthesis of these nucleotides.
**Why the Correct Answer is Right**
The side effects of methotrexate mimic those of folic acid deficiency, which is characterized by megaloblastic anemia, neutropenia, thrombocytopenia, and mucosal ulcers. The mechanism of action of methotrexate involves the depletion of THF, which is necessary for the synthesis of DNA and RNA. As a result, cells in the body are unable to divide properly, leading to the characteristic symptoms of folic acid deficiency.
**Why Each Wrong Option is Incorrect**
**Option A:** Vitamin B12 deficiency also causes megaloblastic anemia, but the underlying mechanism is different from methotrexate toxicity. Vitamin B12 is necessary for the synthesis of methionine from homocysteine, whereas methotrexate directly inhibits DHFR.
**Option B:** Vitamin K deficiency is associated with bleeding disorders, such as easy bruising and bleeding, which is not a characteristic side effect of methotrexate.
**Option C:** Vitamin E deficiency is associated with neurological symptoms, such as ataxia and weakness, which is not a characteristic side effect of methotrexate.
**Clinical Pearl / High-Yield Fact**
Methotrexate should be used with caution in patients with pre-existing folic acid deficiency, as it can exacerbate the symptoms of megaloblastic anemia.
**Correct Answer:** C.