Test Code METH Methylmalonic Acid (MMA), Quantitative, Serum
|Mayo Test ID|
Reporting NameMethylmalonic Acid, QN, S
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.
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Performing LaboratoryMayo Medical Laboratories in Rochester
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1.5 mL
Forms: If not ordering electronically, complete, print, and send a General Request Form (T239) with the specimen (http://www.mayomedicallaboratories.com/media/customer-service/forms/general-request-form.pdf).
Specimen Minimum Volume
Specimen Stability Information
|Serum||Refrigerated (preferred)||48 days|
Reject Due To
Mild OK; Gross OK
Mild OK; Gross OK
Mild OK; Gross OK
Day(s) and Time(s) Performed
Monday through Friday; Continuous until noon
CPT Code Information
LOINC Code Information
|Result ID||Reporting Name||LOINC Code|
|80289||Methylmalonic Acid, QN, S||In Process|
Elevated levels of methylmalonic acid (MMA) result from inherited defects of enzymes involved in MMA metabolism or inherited or acquired deficiencies of vitamin B12 or its downstream metabolites. 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.
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.
Diet, nutritional status, and age should be considered in the evaluation of serum or urine methylmalonic acid level.
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, Supplement 1, S44)
Analytic Time3 days (not reported on Saturday or Sunday)
Test ClassificationThis 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.
- Methylmalonic Acidemia (MMA)