Methylmalonic Acid (MMA)

Methylmalonic acid (MMA) testing is a unique tool for assessing vitamin B12 status, particularly in pregnancy when deficiencies can have significant health implications. Elevated MMA levels often indicate functional B12 deficiency, even when serum B12 levels appear normal. This article discusses the role of MMA testing in pregnancy, its reference ranges, and common causes of elevated levels to support better maternal and fetal outcomes.

Methylmalonic Acid Testing

The methylmalonic acid (MMA) test measures the amount of MMA in a sample. This can be tested via serum/plasma or through a urine test in ratio to creatinine.

Methylmalonic acid is a derivative of malonic acid in which one of the methylene hydrogens is replaced by a methyl group. L-methylmalonyl-CoA is then isomerized to form succinyl-CoA. This reaction is catalyzed by the enzyme methylmalonyl-CoA mutase, which requires adenocobalamin. This reaction is reversible. Succinyl-CoA enters the Krebs cycle, where it is converted to succinate, releasing energy. A dysfunction in the isomerization step can cause an increase in methylmalonic acid. MMA is excreted through the urine. 

Serum, Plasma

The cutoff for MMA in the diagnosis of vitamin B12 deficiency has not been universally agreed upon. Upper ranges can vary between >250 and >350 as diagnostic of
​vitamin B12 deficiency.

Urine

Methylmalonic Acid in Pregnancy

There is a gradual increase in methylmalonic acid levels throughout pregnancy, with a peak in the third trimester. There is a twofold increase in the need for vitamin B12 by the third trimester, with much of this being distributed to the fetus. Maternal vitamin B12 stores are depleted, thus causing a normal elevation in methylmalonic acid. In addition, there are changes in renal excretion of MMA.

Postpartum research on MMA levels is limited, but some studies suggest a sharp decrease in both serum and urinary methylmalonic acid immediately after delivery.

High Methylmalonic Acid in Pregnancy

​Amniotic fluid and maternal urine MMA concentrations in the middle term of neural-tube defect (NTD)-affected pregnancies (22.1 +/- 12.6 nmol/mmol creatinine) were significantly higher than that of normal pregnancies (2.5 +/- 1.1 nmol/mmol creatinine).

One study from Turkey found that 36% of the women tested had urinary MMA levels >6 μmol/mmol crt. Of those, 50% had serum vitamin B12 levels <180 pg/mL.

Most Common Causes of High Methylmalonic Acid in Pregnancy

• Vitamin B12 Deficiency 
• Kidney Disease
• Genetics
• Nutritional Deficiencies (vitamin B7 (Biotin), bicarbonate)

Only 22% of elevated MMA cases can be attributed to overt cobalamin
(vitamin B12) deficiency, yet elevated MMA and homocysteine are found in
98% of vitamin B12 deficiency cases.

Low Methylmalonic Acid in Pregnancy

​Not considered pathogenic

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Medical Disclaimer:
This content is for educational purposes only and is intended for licensed medical professionals. It is based on current research, subject to change, and not intended to diagnose, treat, or prevent any medical condition. This information does not replace consultation with a qualified healthcare provider. Seek professional medical evaluation and treatment from a licensed provider. Use of this information is at your own risk.​

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