Is an MMA Level of 750 nmol/L Extreme?
Yes, an MMA level of 750 nmol/L is markedly elevated and indicates severe functional vitamin B12 deficiency requiring immediate treatment. This level is nearly 3 times the upper limit of normal and demands urgent intervention.
Understanding the Severity of This Result
- Normal MMA levels are below 270-271 nmol/L, and any elevation above this threshold indicates functional vitamin B12 deficiency or metabolic disease 1
- Your level of 750 nmol/L is 2.8 times higher than the diagnostic threshold, placing you in the range of severe functional B12 deficiency 1
- This degree of elevation is clinically significant and associated with active cellular B12 depletion, regardless of what your serum B12 level shows 2, 1
What This Level Means Clinically
Functional deficiency is confirmed - MMA above 271 nmol/L indicates that your cells lack adequate B12 to function properly, even if serum B12 appears normal 1
Immediate treatment is warranted - At this level of elevation, you should begin B12 replacement therapy without delay to prevent irreversible neurological damage 2, 1
This is NOT genetic methylmalonic acidemia - In the rare genetic form of methylmalonic acidemia (an enzymatic defect), MMA levels are typically >1,000 nmol/L and present with life-threatening ketoacidotic coma 1, 3. Your level of 750 nmol/L, while elevated, is consistent with severe acquired B12 deficiency rather than the genetic disorder 1
Critical Considerations Before Finalizing Diagnosis
Renal function must be evaluated - Kidney disease elevates MMA independent of B12 status, potentially causing false-positive results 2, 1, 4
- If your eGFR is <60 mL/min, the MMA elevation may be partially explained by impaired renal clearance 4
- In patients with low-normal B12 and decreased kidney function, unadjusted MMA overestimates B12 deficiency by 40% 4
- However, even accounting for renal impairment, an MMA of 750 nmol/L still suggests significant functional deficiency 4
Recommended Immediate Actions
Begin B12 replacement therapy now - Do not delay treatment while investigating the underlying cause 2, 1
- Oral B12 1,000-2,000 mcg daily is effective for most patients 5
- Intramuscular B12 should be considered if you have severe neurological symptoms (numbness, weakness, cognitive changes, ataxia) or confirmed malabsorption 2, 5
Identify the underlying cause - Common causes of severe functional B12 deficiency include:
- Pernicious anemia (autoimmune destruction of intrinsic factor) 2, 5
- Atrophic gastritis or prolonged use of acid-suppressing medications 2, 5
- Malabsorption from bariatric surgery, celiac disease, or inflammatory bowel disease 5
- Strict vegan diet without supplementation 2
- Medications including metformin (>4 months use), colchicine, or anticonvulsants 5
Monitor for neurological complications - Neurological symptoms often appear before anemia and can become irreversible if untreated 5, 6
- Watch for cognitive difficulties, memory problems, peripheral neuropathy, weakness, or gait disturbances 5, 6
- MMA concentrations are more strongly associated with poor functional performance and muscle weakness than serum B12 alone 6
Common Pitfalls to Avoid
Do not wait for serum B12 results to guide treatment - Up to 50% of patients with elevated MMA have "normal" serum B12 levels, yet still have functional cellular deficiency 2, 5
Never give folic acid before treating B12 deficiency - Folic acid can mask the anemia of B12 deficiency while allowing irreversible neurological damage to progress 5
Do not assume dietary deficiency alone - An MMA this elevated typically indicates malabsorption rather than simple dietary insufficiency, requiring investigation for pernicious anemia or other absorptive disorders 2, 5