Signs and Symptoms of Vitamin B12 Deficiency
Vitamin B12 deficiency presents with a broad spectrum of hematological, neurological, psychiatric, and gastrointestinal manifestations that can occur independently or in combination, with neurological symptoms often appearing before hematological changes. 1, 2, 3
Hematological Signs
- Macrocytic anemia with elevated mean corpuscular volume (MCV), though anemia may be absent in up to one-third of cases 2, 4
- Hypersegmented neutrophils on peripheral blood smear, resulting from impaired DNA synthesis affecting rapidly dividing bone marrow cells 5
- Symptoms of anemia including fatigue, dyspnea on exertion, angina, and signs of congestive heart failure (ankle edema, orthopnea, nocturia) 4
- Anemia that fails to respond to iron supplementation should raise suspicion for B12 deficiency 2
Neurological Manifestations
Neurological symptoms are particularly critical because they can become irreversible if untreated for longer than 3 months, and they frequently precede hematological abnormalities. 6, 3, 4
Peripheral Nervous System
- Peripheral neuropathy with pins and needles, numbness, or paresthesia in extremities 2, 7
- Tingling sensations affecting hands and feet 7
- Neuropathic pain 8
Spinal Cord (Subacute Combined Degeneration)
- Symmetric dysesthesia and disturbance of position sense (impaired proprioception) 4
- Sensory ataxia leading to balance problems, gait disturbances, and increased fall risk 2, 4
- Spastic paraparesis or tetraparesis in advanced cases 4
- MRI findings show symmetrical increased T2 signal intensity in posterior and lateral columns of cervical and thoracic spinal cord 4
Visual System
- Optic neuropathy presenting as symmetric, painless, progressive visual loss or blurred vision 2, 4, 7
Motor Symptoms
- Hypotonia, particularly in pediatric patients 7
- Inability to sit or walk without support 7
- Hand tremor 7
Neuropsychiatric Symptoms
- Cognitive impairment including memory problems, concentration difficulty, and slow mentation 2, 3, 7, 8
- Dementia or dementia-like symptoms in elderly patients 4, 8
- Depression and depressive symptoms 3, 8
- Brain fog and attention deficits 3, 4
- Disorientation 8
Other Clinical Features
- Glossitis (inflammation of the tongue) 2
- Severe fatigue that is disproportionate to other findings 3, 7, 8
- Syncope and dizziness 7
- Convulsions (particularly in pediatric cases) 7
Critical Clinical Pitfalls
A major pitfall is that normal serum B12 levels do not exclude functional B12 deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid (MMA). 9 Testing should include MMA or active B12 (holotranscobalamin) when clinical suspicion is high despite normal total B12 levels. 1, 9, 3
Another critical error is administering folic acid before or without B12 treatment, which can mask the anemia while allowing irreversible neurological damage to progress (subacute combined degeneration of the spinal cord). 2, 6 Always treat B12 deficiency immediately before initiating folic acid supplementation. 2
Neurological symptoms can be nonspecific and easily attributed to aging or comorbid conditions in elderly patients, leading to delayed diagnosis and potentially irreversible damage. 8 Maintain high clinical suspicion in at-risk populations even with borderline or normal B12 levels. 9, 8