Methylmalonic Acid (MMA), Quantitative, Serum
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Methylmalonic Acid, QN, S
Methylmalonic Acid (MMA)
MMA (Methylmalonic Acid)
Methylmalonic Acid (MMA)
MMA (Methylmalonic Acid)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1.5 mL
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross OK
Mild OK; Gross OK
Mild OK; Gross OK
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Serum||Refrigerated (preferred)||48 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 acidemias, which include at least 9 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. The final 2, CblE and CblG deficiencies, cause impaired synthesis of the enzymes methionine synthase and methionine synthase reductase and are not associated with abnormal MMA concentrations.
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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =0.40 nmol/mL
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 Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Diet, nutritional status, and age should be considered in the evaluation of serum or urine methylmalonic acid level.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Fenton WA, Gravel RA, Rosenblatt DS: Disorders of propionate and methylmalonate metabolism. In The Metabolic and Molecular Bases of Inherited Disease. In Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, A Beaudet, B Vogelstein, et al. McGraw-Hill. Chapter 94. Retrieved 2010
2. Klee GG: Cobalamin and folate evaluation measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem 2000:46(8):1277-1283
3. Hussein L, Abdel A, Tapouzada S, Boehles H: Serum vitamin B12 concentrations among mothers and newborns and follow-up study to assess implication on the growth velocity and the urinary methylmalonic acid excretion. Int J Vitam Nutr Res. 2009 Sep:79(5-6):297-307
Method Description Describes how the test is performed and provides a method-specific reference
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)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; Continuous until noon
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
3 days (not reported on Saturday or Sunday)
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|80289||Methylmalonic Acid, QN, S||13964-2|