What tests should be run to confirm a suspected vitamin B deficiency in an adult patient with tingling and numbness on the tip of the tongue?

Diagnostic Testing for Suspected Vitamin B12 Deficiency with Tongue Paresthesia

For an adult with tingling/numbness of the tongue tip and suspected vitamin B12 deficiency, start with serum total vitamin B12 as the initial test, followed by methylmalonic acid (MMA) testing if results are indeterminate (180-350 pg/mL), to confirm functional deficiency. 1

Initial Testing Strategy

Begin with serum total vitamin B12 as your first-line test, which costs approximately £2 with rapid turnaround in local laboratories. 1 This test should be accompanied by a complete blood count to assess for macrocytic anemia, though anemia may be absent in one-third of cases. 1, 2

Interpretation of Total B12 Results:

• <180 pg/mL (<133 pmol/L): Confirms deficiency—proceed directly to treatment 1
• 180-350 pg/mL (133-258 pmol/L): Indeterminate range—measure MMA to confirm functional deficiency 1
• >350 pg/mL (>258 pmol/L): Makes deficiency unlikely, but consider functional markers if high clinical suspicion remains 1

Confirmatory Testing with Methylmalonic Acid

When B12 results fall in the indeterminate range (180-350 pg/mL), measure serum methylmalonic acid to identify functional B12 deficiency that reflects actual cellular B12 status. 1 This is critical because standard serum B12 testing misses functional deficiency in up to 50% of cases—the Framingham Study found that 12% had low serum B12, but an additional 50% had elevated MMA indicating metabolic deficiency despite "normal" serum levels. 1

MMA Interpretation:

• MMA >271 nmol/L: Confirms functional B12 deficiency with 98.4% sensitivity 1
• MMA testing costs £11-80 per test and is cost-effective at £3,946 per quality-adjusted life year when used after indeterminate B12 results 1

Alternative Testing: Active B12 (Holotranscobalamin)

Active B12 measures the biologically active form available for cellular use and is more accurate than total B12, but costs £18 per test with longer turnaround times. 1 If using active B12 as your initial test:

• <25 pmol/L: Confirms deficiency 1
• 25-70 pmol/L: Indeterminate—requires MMA testing 1
• >70 pmol/L: Makes deficiency unlikely 1

Additional Diagnostic Considerations

Homocysteine Testing

While homocysteine >15 μmol/L supports B12 deficiency diagnosis, it is less specific than MMA and can be elevated in folate deficiency (91% of cases) as well. 1 The pattern helps differentiate:

• Elevated homocysteine + elevated MMA = B12 deficiency 1
• Elevated homocysteine + normal MMA = folate deficiency 1

Etiologic Testing

Once deficiency is confirmed, consider testing for the underlying cause:

• Intrinsic factor antibodies for pernicious anemia (if positive, lifelong treatment is necessary) 1
• Gastrin levels if pernicious anemia suspected (markedly elevated >1000 pg/mL indicates the condition) 1
• Anti-parietal cell antibodies for autoimmune gastritis 3

Critical Clinical Pitfalls to Avoid

Never administer folic acid before treating B12 deficiency, as it may mask anemia while allowing irreversible neurological damage to progress. 1, 4 Vitamin B12 deficiency that progresses for longer than three months may produce permanent degenerative lesions of the spinal cord. 4

Do not rely solely on serum B12 to rule out deficiency, especially in patients >60 years where metabolic deficiency is common despite normal serum levels—18.1% of patients >80 years have metabolic B12 deficiency. 1

Consider medication-induced deficiency: Metformin use >4 months, proton pump inhibitors or H2 blockers >12 months, colchicine, anticonvulsants, and pregabalin can all interfere with B12 absorption or utilization. 1, 2, 5

Special Considerations for Your Patient

Symmetric paresthesia (including tongue tingling/numbness) is a common neurological manifestation of vitamin B12 deficiency representing peripheral nerve damage. 2 Neurologic symptoms often present before hematologic changes and can become irreversible if untreated. 1 This makes prompt and accurate diagnosis essential.

If you have already started B12 supplementation, measure MMA as the primary test when patients are taking supplements, as this functional marker reflects actual cellular B12 status regardless of supplementation. 1 Serum B12 testing after supplementation has begun is unreliable.