A 62-year-old man presents to the clinic complaining of progressive numbness and a pins-and-needles sensation in his feet that has ascended to his mid-calves over the past six months. He also notes increased difficulty with balance, particularly when walking in the dark. His medical history is significant for vitiligo and hypothyroidism. He takes levothyroxine. Vital signs are within normal limits. Physical examination reveals a beefy, red, smooth tongue and decreased vibratory and proprioceptive sensation in the lower extremities. Laboratory studies show a hemoglobin of 8.4 g/dL, a mean corpuscular volume (MCV) of 114 fL, and a reticulocyte count of 0.5%.
Which of the following laboratory findings is most likely to be present in this patient?
The correct answer is:
D) Increased serum homocysteine and increased methylmalonic acid
This patient presents with megaloblastic anemia and subacute combined degeneration of the spinal cord (SCD), which are hallmarks of vitamin B12 (cobalamin) deficiency. Vitamin B12 serves as a cofactor for two critical metabolic reactions: the conversion of homocysteine to methionine and the conversion of methylmalonyl-CoA to succinyl-CoA. When B12 is deficient, both homocysteine and methylmalonic acid (MMA) accumulate in the serum. This is a key diagnostic differentiator from folate deficiency, in which homocysteine levels are elevated but MMA levels remain normal. The neurological symptoms (paresthesias, loss of proprioception/vibration) are specifically attributed to the accumulation of MMA and its precursors, which interfere with normal myelin synthesis in the dorsal columns and lateral corticospinal tracts.
Answer choice A: Decreased serum homocysteine and decreased methylmalonic acid, is incorrect. Both markers increase in the setting of B12 deficiency due to the loss of the enzymatic pathways that utilize them.
Answer choice B: Decreased serum homocysteine and increased methylmalonic acid, is incorrect. Homocysteine will be elevated in B12 deficiency as its conversion to methionine is impaired.
Answer choice C: Increased serum homocysteine and decreased methylmalonic acid, is incorrect. This pattern is characteristic of folate deficiency. Folate deficiency causes megaloblastic anemia but does not cause the neurologic deficits seen in this patient.
Answer choice E: Normal serum homocysteine and normal methylmalonic acid, is incorrect. These markers are highly sensitive for B12 deficiency. If both were normal, it would effectively rule out a functional deficiency of cobalamin as the cause of the patient's symptoms.
Key Learning Point
Vitamin B12 deficiency is characterized by macrocytic anemia (MCV > 100 fL), hypersegmented neutrophils, and neurologic symptoms due to demyelination. Laboratory confirmation involves finding elevated levels of both homocysteine and methylmalonic acid. In contrast, folate deficiency presents with elevated homocysteine only.
