Question

Difficulty: EasyHematology and Oncology

A 62-year-old woman is evaluated for progressively worsening fatigue and dyspnea on exertion over the past 3 months. She has followed a strict vegan diet for the past 5 years and does not take any nutritional supplements. Physical examination reveals pale conjunctivae, a smooth and red tongue, and decreased vibratory sensation in the lower extremities bilaterally. Laboratory studies show:

TestResultReference Range
Hemoglobin9.2 g/dL12.0-15.5 g/dL
Mean corpuscular volume114 fL80-100 fL

Which of the following additional laboratory findings is most likely to be present in this patient?

  1. Elevated methylmalonic acid and elevated homocysteineAnswer
  2. B
    Normal methylmalonic acid and elevated homocysteine
  3. C
    Decreased serum ferritin and elevated total iron-binding capacity
  4. D
    Positive direct antiglobulin test and elevated reticulocyte count
  5. E
    Normal methylmalonic acid and normal homocysteine

Answer

Elevated methylmalonic acid and elevated homocysteine
The patient's strict vegan diet, macrocytic anemia (MCV > 100 fL), glossitis, and neurologic symptoms (decreased vibratory sensation) are classic for vitamin B12 (cobalamin) deficiency. Vitamin B12 is a required cofactor for two major reactions: the conversion of methylmalonyl-CoA to succinyl-CoA and the conversion of homocysteine to methionine. Therefore, a deficiency in vitamin B12 leads to the accumulation and elevated serum levels of both methylmalonic acid and homocysteine.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and diet history.
The patient has fatigue, a strict vegan diet, glossitis (smooth, red tongue), and neurologic symptoms (decreased vibratory sensation).
Identifying the clinical syndrome helps narrow down the etiology of the anemia.
2
Interpret the initial laboratory findings.
Hemoglobin is low (9.2 g/dL) and MCV is elevated (114 fL), indicating a macrocytic anemia.
Macrocytic anemias are commonly caused by vitamin B12 or folate deficiency, liver disease, or alcohol use.
3
Differentiate between the causes of macrocytic anemia based on symptoms.
The presence of neurologic symptoms (decreased vibratory sensation) points to vitamin B12 deficiency rather than folate deficiency.
Vitamin B12 is essential for myelin synthesis, and its deficiency leads to subacute combined degeneration of the spinal cord.
4
Determine the expected confirmatory laboratory findings.
Vitamin B12 deficiency results in the elevation of both methylmalonic acid and homocysteine.
Vitamin B12 is a cofactor for the conversion of methylmalonyl-CoA to succinyl-CoA and homocysteine to methionine.

Key Concept

Patients with a strict vegan diet are at risk for vitamin B12 deficiency, which presents with macrocytic anemia, glossitis, and neurologic deficits, and is confirmed by elevated levels of both methylmalonic acid and homocysteine.
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