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Test Code METH Methylmalonic Acid (MMA), Quantitative, Serum

Additional Test Codes

Mayo Test ID
MMAS

Reporting Name

Methylmalonic Acid, QN, S

Useful For

Evaluating children with signs and symptoms of methylmalonic acidemia

 

Additional confirmatory testing must be performed.

 

Evaluating individuals with signs and symptoms associated with a variety of causes of cobalamin (vitamin B12) deficiency

 

Several studies have suggested that the determination of serum or urinary methylmalonic acid could be a more reliable marker of cobalamin deficiency than direct cobalamin determination.

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum

Specimen Required

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1.5 mL

Specimen Minimum Volume

0.8 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 48 days
  Ambient  48 days
  Frozen  48 days

Reject Due To

Hemolysis

Mild OK; Gross OK

Lipemia

Mild OK; Gross OK

Icterus

Mild OK; Gross OK

Other

NA

Reference Values

≤0.40 nmol/mL

Day(s) and Time(s) Performed

Monday through Friday; Continuous until noon

CPT Code Information

83921

LOINC Code Information

Result ID Reporting Name LOINC Code
80289 Methylmalonic Acid, QN, S 13964-2

Clinical Information

The concentration of serum methylmalonic acid (MMA) is elevated primarily in patients affected with methylmalonic acidemia and patients with a nutritional deficiency of cobalamin (vitamin B12) or folic acid. Of the 2, nutritional deficiencies are much more common and can be due to intestinal malabsorption, impaired digestion, or poor diet. Elderly patients with cobalamin deficiency may present with peripheral neuropathy, ataxia, loss of position and vibration senses, memory impairment, depression, and dementia in the absence of anemia. Other conditions such as renal insufficiency, hypovolemia, and bacterial overgrowth of the small intestine also contribute to the possible causes of mild methylmalonic acidemia and aciduria.

 

MMA is also a specific diagnostic marker for the group of disorders collectively called methylmalonic acidemia, which include at least 7 different complementation groups. Two of them (mut0 and mut-) reflect deficiencies of the apoenzyme portion of the enzyme methylmalonyl-CoA mutase. Two other disorders (CblA and CblB) are associated with abnormalities of the adenosylcobalamin synthesis pathway. CblC, CblD, and CblF deficiencies lead to impaired synthesis of both adenosyl- and methylcobalamin.

 

Since the first reports of this disorder in 1967, many hundreds of cases have been diagnosed worldwide. Newborn screening identifies approximately 1 in 30,000 live births with a methylmalonic acidemia. The most frequent clinical manifestations are neonatal or infantile metabolic ketoacidosis, failure to thrive, and developmental delay. Excessive protein intake may cause life-threatening episodes of metabolic decompensation and remains a life-long risk unless treatment is closely monitored, including serum and urine MMA levels.

Interpretation

In pediatric patients, markedly elevated methylmalonic acid values indicate a probable diagnosis of methylmalonic acidemia. Additional confirmatory testing must be performed.

 

In adults, moderately elevated values indicate a likely cobalamin (vitamin B12) deficiency.

Cautions

Diet, nutritional status, and age should be considered in the evaluation of serum or urine methylmalonic acid level.

Method Description

Methylmalonic acid (MMA) is determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) stable isotope dilution analysis. The specimen is mixed with an internal standard (methyl-d3-malonic acid; d3-MMA, 0.2 nmol). MMA and d3-MMA are isolated by automated strong anion-exchange solid phase extraction. LC-MS/MS is performed using mobile phases composed of acetonitrile/0.4% aqueous formic acid and water/0.4% aqueous formic acid (5/95, v:v) using a short C18 column (C18, 50 mm x 4.6 mm, 5 micron) to separate MMA and d3-MMA from the bulk of the specimen matrix. The MS/MS is operated in the multiple reaction monitoring (MRM) negative mode to follow the precursor to product species transitions 117 m/z to 73 m/z and 120 m/z to 76 m/z for MMA and d3-MMA respectively. Separation of MMA/d3-MMA from the more physiologically abundant succinic acid is accomplished by the careful selection of MRM transitions and optimization of the LC separation. The ratios of the extracted peak areas of MMA to d3-MMA determined by LC-MS/MS are used to calculate the concentration of MMA present in the sample.(Lacey J, Magera MJ, Matern M: Methylmalonic acid quantitation in serum, urine and amniotic fluid: a method modification with benefits. J Am Soc Mass Spec 2010:21[5], Supplement 1, S44)

Analytic Time

3 days (not reported on Saturday or Sunday)

Disease States

  • Homocystinuria
  • Methylmalonic Acidemia (MMA)

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.