This patient has folate deficiency. Folate deficiency caused by decreased folate consumption occurs infrequently, because normal diets are replete with folate. However, patients with folate-deficient diets, especially those with generalized malnutrition or poor nutrition, can become folate deficient in weeks to months because of relatively limited stores of folate in the body. Other less common causes of folate deficiency include conditions such as hemolytic anemia (for example, sickle cell disease), desquamating skin disorders (for example, psoriasis), and other conditions associated with increased cellular turnover. Measuring serum folate levels is typically unreliable in diagnosing folate deficiency, because folate levels increase rapidly after a single folate-containing meal. Plasma homocysteine levels increase in folate deficiency, whereas homocysteine and methylmalonic acid levels are increased in cobalamin deficiency. An elevated homocysteine level has a sensitivity of greater than 90% in the diagnosis of folate deficiency, making homocysteine measurement a reasonable test when the disorder is suspected but the serum folate level is normal.

In addition to peripheral blood smear findings of microcytosis and anisopoikilocytosis (abnormalities in erythrocyte size and shape), patients with iron deficiency have reduced serum iron and ferritin levels, increased total iron-binding capacity, and reduced transferrin saturation (iron/total iron-binding capacity). The patient's macrocytosis and high homocysteine level make iron deficiency an unlikely cause of her anemia.

α-Thalassemia trait (or α-thalassemia minor) is associated with mild anemia, microcytosis, hypochromia, target cells on the peripheral blood smear, and, in adults, normal hemoglobin electrophoresis results. The (-α/-α) variant is found in 2% to 3% of all black persons and is often mistaken for iron deficiency. The patient's new-onset macrocytic anemia is not consistent with an inherited hemoglobinopathy associated with microcytosis.

Vitamin B₁₂ deficiency usually develops over several months, not weeks. Furthermore, homocysteine and methylmalonic acid levels are elevated in vitamin B₁₂ deficiency, but this patient's methylmalonic acid level is normal.