A 43-year-old woman presents with dizziness, chronic fatigue, peripheral tingling of the arms and fingers, neck pain, headache, a platelet count of 471 × 10⁹/L, and a serum vitamin B12 level of 214 pg/mL. What is the most likely diagnosis?

Vitamin B12 Deficiency

This patient has vitamin B12 deficiency causing her constellation of neurological symptoms (dizziness, chronic fatigue, peripheral tingling), and the thrombocytosis is likely reactive rather than a primary hematologic disorder. 1, 2

Diagnostic Interpretation

The serum B12 level of 214 pg/mL falls in the indeterminate range (180-350 pg/mL) and requires methylmalonic acid (MMA) testing to confirm functional deficiency. 1 However, given the clear neurological symptoms—which are classic for B12 deficiency—treatment should be initiated immediately while awaiting confirmatory testing. 1, 3

Key Laboratory Findings

• B12 of 214 pg/mL is indeterminate but concerning: This level sits in the gray zone where up to 50% of patients have functional metabolic deficiency despite "normal" serum levels when measured by MMA. 1, 3

• Platelet count of 471 × 10⁹/L represents thrombocytosis: This is likely reactive (secondary to inflammation, iron deficiency, or other causes) rather than related to B12 deficiency, which typically causes thrombocytopenia when severe. 4, 5

Clinical Symptom Correlation

The patient's symptoms are highly characteristic of B12 deficiency:

• Peripheral tingling in arms and fingers: This represents peripheral neuropathy affecting sensory pathways, which often appears before motor dysfunction and can occur even with borderline B12 levels. 2, 3

• Chronic fatigue and dizziness: These are common early manifestations of functional B12 deficiency. 1, 2

• Neck pain and headache: While less specific, these can accompany the neurological manifestations of B12 deficiency. 2

Critical point: Neurological symptoms often appear before hematological changes (anemia, macrocytosis) develop, and up to one-third of B12-deficient patients never develop anemia. 1, 3

Recommended Diagnostic Algorithm

1. Order MMA testing immediately to confirm functional B12 deficiency (target: MMA >271 nmol/L confirms deficiency). 1

2. Check complete blood count with peripheral smear to assess for macrocytosis (MCV >98 fL), hypersegmented neutrophils, or anemia—though their absence does not exclude deficiency. 1, 2

3. Measure homocysteine if MMA is unavailable or to support the diagnosis (target: >15 μmol/L suggests tissue deficiency). 1

4. Screen for underlying causes:

   • Anti-intrinsic factor antibodies and anti-parietal cell antibodies for pernicious anemia 1, 4
   • Assess for medications interfering with B12 absorption (metformin >4 months, PPIs >12 months, H2 blockers, colchicine, phenobarbital, pregabalin) 1, 2
   • Screen for autoimmune conditions (thyroid disease, type 1 diabetes) which frequently coexist 1

5. Obtain iron studies (ferritin, transferrin saturation, CRP) to explain the thrombocytosis and assess for concurrent iron deficiency. 2

Immediate Treatment Recommendation

Do not wait for MMA results to initiate treatment given the clear neurological symptoms. 1, 2

Treatment Protocol for Neurological Involvement

Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg IM every 2 months for life. 2 This aggressive regimen is essential because neurological damage can become irreversible if treatment is delayed. 2, 3

Alternative if Malabsorption Not Confirmed

If testing ultimately shows no malabsorption and symptoms are mild, oral B12 1000-2000 mcg daily is equally effective for most patients. 1 However, given the neurological symptoms, intramuscular therapy is safer initially. 2

Critical Pitfalls to Avoid

• Never rely solely on serum B12 to rule out deficiency: Standard testing misses functional deficiency in up to 50% of cases, particularly in patients with neurological symptoms. 1, 3

• Never give folic acid before treating B12 deficiency: This can mask anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress. 1, 2

• Do not delay treatment waiting for confirmatory tests: Neurological symptoms mandate immediate therapy, as damage can become permanent. 2, 3

• Do not assume normal CBC excludes B12 deficiency: Macrocytic anemia is absent in one-third of cases, and neurological symptoms often precede hematological changes. 1, 3

Monitoring Response

• Recheck B12 and MMA at 3-6 months to confirm normalization (target B12 >300 pmol/L, MMA <271 nmol/L). 1

• Monitor for reticulocytosis at days 5-10: Absence of reticulocyte response should prompt hematology referral for alternative diagnoses. 2

• Assess symptom improvement: Neurological symptoms should begin improving within weeks, though complete resolution may take months. 1, 3

• Annual B12 screening thereafter if autoimmune cause is confirmed, as these patients require lifelong treatment. 1