What is the diagnosis in a 72-year-old woman with hemoglobin 10.2 g/dL, mean corpuscular volume (MCV) 102 fL, neutrophilia on blood smear, ferritin 220 ng/mL, vitamin B12 210 pg/mL, folate 12 ng/mL, and methylmalonic acid 580 nmol/L?

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Last updated: September 26, 2026 • View editorial policy

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Diagnosis: Vitamin B12 Deficiency (Cobalamin Deficiency)

This 72-year-old woman has vitamin B12 deficiency confirmed by the elevated methylmalonic acid (580 nmol/L), despite a low-normal serum B12 level of 210 pg/mL. 1

Diagnostic Reasoning

The clinical picture clearly points to B12 deficiency through the following algorithmic approach:

Step 1: Classify the Anemia by MCV

  • MCV 102 fL = Macrocytic anemia 2, 3
  • This immediately narrows the differential to: vitamin B12 deficiency, folate deficiency, myelodysplastic syndrome, medications (azathioprine, hydroxyurea), hypothyroidism, or alcoholism 2, 3

Step 2: Evaluate Vitamin Levels

  • Folate 12 ng/mL = Normal (rules out folate deficiency)
  • Vitamin B12 210 pg/mL = Low-normal range 1

Critical point: Patients with B12 levels in the low-normal range (200-500 pg/mL) may still be functionally deficient and manifest hematologic, neurologic, or psychiatric symptoms 1. Between 2.2-8% of patients with polyneuropathy have B12 deficiency based on elevated metabolites alone, and 44% of B12-deficient patients have normal serum B12 but abnormal metabolites 4.

Step 3: Confirm with Metabolites

  • Methylmalonic acid 580 nmol/L = ELEVATED (normal <280 nmol/L)
  • This confirms true B12 deficiency 1, 4, 1

Methylmalonic acid is elevated in 98.4% of B12-deficient patients and is more specific than homocysteine (which can be elevated in folate deficiency, pyridoxine deficiency, renal insufficiency, and hypothyroidism) 4.

Step 4: Rule Out Other Causes of Macrocytosis

  • Ferritin 220 ng/mL = Normal (rules out iron deficiency as primary cause) 3
  • The neutrophilia on blood smear may represent a reactive process but does not explain the macrocytic anemia

Important Caveats

The normal MCV does not rule out B12 deficiency. In fact, microcytosis and macrocytosis can coexist (e.g., combined iron and B12 deficiency), neutralizing each other to produce a falsely normal MCV 3. However, this patient has clear macrocytosis at 102 fL.

Folate fortification does not mask macrocytic anemia in B12 deficiency, though high folate supplement use might 1. This patient actually demonstrates the expected pattern: higher folate levels in B12-deficient patients are associated with more severe anemia and cognitive impairment 1.

Underlying Etiology to Investigate

In a 72-year-old woman, the most likely causes are:

  • Pernicious anemia (autoimmune destruction of parietal cells, lack of intrinsic factor) 1
  • Atrophic gastritis with achlorhydria (affects ~15% of adults over 60) 1
  • Malabsorption of food-protein-B12 complex 1

Check anti-intrinsic factor antibodies and anti-parietal cell antibodies to confirm pernicious anemia 5, 6.

Treatment Implications

Initiate parenteral vitamin B12 replacement immediately (1,000 µg intramuscularly, subcutaneously, or intranasally) if pernicious anemia is confirmed or suspected 1. Oral B12 (1,000 µg/day) can be used for other causes of B12 deficiency without malabsorption 1.

The elevated methylmalonic acid definitively establishes the diagnosis and mandates treatment to prevent irreversible neurologic damage, even though the patient's B12 level appears "borderline" 1, 4, 1, 6.

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