Clues Pointing TO This Diagnosis

Twenty-year strict vegan diet — animal-source foods are the only dietary source of B12, so long-term veganism without supplementation is a classic cause of dietary deficiency
Age 67 — older adults are at higher risk for B12 deficiency and its cognitive manifestations
Symmetric distal paresthesias beginning in the feet — sensory symptoms/paresthesias are among the earliest and most common neurologic features
Ascending numbness — progressive demyelination produces spreading sensory loss
Gait instability and stumbling in the dark — loss of proprioception with worsening in low light reflects dorsal column involvement
Positive Romberg sign — indicates impaired proprioception from posterior column degeneration
Impaired vibration and proprioceptive sensation — hallmark of subacute combined degeneration of the posterior/lateral columns
Cognitive "brain fog"/memory decline — B12 deficiency causes reversible cognitive impairment, especially in older adults
Macrocytic anemia with elevated MCV — megaloblastic changes from impaired DNA synthesis
Hypersegmented neutrophils on smear — characteristic megaloblastic peripheral-blood finding
Very low (undetectable) serum B12 — a markedly low level strongly supports true deficiency
Symptoms developing after years of dietary lack — neurologic sequelae take 2–5 years to appear because of large hepatic B12 stores

Why It's NOT the Similar Diseases

NOT folate deficiency — folate deficiency also causes megaloblastic anemia but does not produce subacute combined degeneration; Mortimer's prominent neurologic signs (proprioceptive loss, Romberg) point to B12, and B12 is the documented low value
NOT pernicious anemia — pernicious anemia results from autoimmune loss of intrinsic factor, whereas Mortimer's cause is clearly dietary from long-term veganism rather than malabsorption
NOT diabetic (or other length-dependent) peripheral neuropathy — typical axonal neuropathies do not cause dorsal-column signs like a positive Romberg and preserved-reflex proprioceptive loss, and would not explain macrocytic anemia
NOT hypothyroidism — hypothyroidism can cause macrocytosis and fatigue but not subacute combined degeneration or hypersegmented neutrophils, and the B12 level is diagnostic here
NOT alcohol/liver-related (nonmegaloblastic) macrocytosis — these raise MCV without megaloblastic changes and without the neurologic myelopathy Mortimer displays

Differential Diagnosis List

Folate deficiency — ruled out by the presence of subacute combined degeneration and a documented low B12
Pernicious anemia — ruled out by a clear dietary etiology (long-term veganism) rather than intrinsic-factor malabsorption
Diabetic/length-dependent peripheral neuropathy — ruled out by dorsal-column signs (positive Romberg) and coexisting macrocytic anemia
Hypothyroidism — ruled out by megaloblastic smear findings and the diagnostic low B12 level
Nonmegaloblastic macrocytosis (alcohol/liver disease) — ruled out by hypersegmented neutrophils and neurologic myelopathy

Key Distinguishing Test

The initial test is a total serum vitamin B12 level; a level below about 180 pg/mL is diagnostic of deficiency, and a markedly low/undetectable level (as in Mortimer) strongly confirms it.
When the B12 level is borderline (180–350 pg/mL), an elevated methylmalonic acid (MMA) confirms functional B12 deficiency and is the more specific confirmatory marker.

Board Note

Only animal-source foods contain B12, so all vegans should supplement (fortified foods or oral tablets) from the start; metformin, PPIs, older age, gastrectomy/ileal resection, and pernicious anemia are other key causes
Neurologic manifestations—paresthesias, ataxia, proprioceptive/vibratory loss, and subacute combined degeneration—can occur before or without anemia, and the severity of anemia is often inversely related to neurologic severity
Confirm with serum B12; use MMA (and homocysteine) for borderline cases, and evaluate unexplained deficiency for atrophic gastritis/pernicious anemia (anti–intrinsic factor and anti–parietal-cell antibodies)
Oral high-dose B12 (typically 1,000–2,000 mcg daily) is effective and noninferior to intramuscular therapy even in malabsorption/pernicious anemia; reserve initial intramuscular therapy for severe deficiency, neurologic involvement, or malabsorption because it corrects levels faster
Treat early—neurologic damage may be irreversible if treatment is delayed—and always check folate and correct B12 before/with folate to avoid masking ongoing neurologic injury
The following NEJM illustration maps the multi-system clinical and laboratory manifestations of B12 deficiency, including the spinal cord changes underlying Mortimer's presentation:
Figure 2. Clinical and Laboratory Findings in Vitamin B12 Deficiency.
Vitamin B12 Deficiency. N Engl J Med. January 9, 2013.
Used under license from The New England Journal of Medicine.

“Mortimer’s Story”