Test ID: MMAAF
Methylmalonic Acid (MMA), Amniotic Fluid
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Specific diagnostic marker for methylmalonic acidemia
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
A Biochemical Genetics Laboratory genetic counselor or consultant approval is required prior to specimen collection. The prenatal diagnosis is made on a dual, complementary approach involving direct chemical determination of MMA (at MML) in cell-free supernatant of amniotic fluid and molecular analysis for previously identified familial mutations or complementation studies (not currently offered at Mayo Medical Laboratories) in cultured amniocytes. Both tests are required for a definitive diagnosis. The amniocentesis must be performed between 16 and 19 weeks of gestational age. Previous knowledge of the complementation group (typically labeled as mut0, mut-, CblA, CblB, CblC, etc), associated homocystinuria, responsiveness to vitamin B12 of the affected child, and B12 intake of the mother during the pregnancy (if receiving treatment) are critical to secure an accurate prenatal diagnosis.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
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
Aliases Lists additional common names for a test, as an aid in searching
Cobalamin
Methylmalonic acidemia
MMA, Amniotic Fluid
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.
Mayo Medical Laboratories’ genetic counselor or consultant approval is required prior to ordering test.
Container/Tube: Amniotic fluid container
Specimen Volume: 5-10 mL
Collection Instructions:
1. Obtain specimen during 16 to 19 weeks of gestation.
2. Draw 25 to 30 mL of amniotic fluid and spin down.
3. Send cell-free supernatant specimen.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Amniotic Fld | Frozen (preferred) | 45 days |
| Refrigerated | 45 days | |
| Ambient | 72 hours |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Methylmalonic acid (MMA) is 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 in the adenosylcobalamin synthesis pathway. CblC, CblD, and CblF deficiencies lead to impaired synthesis of both adenosyl- and methyl-cobalamin. 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.
Because the morbidity and mortality of methylmalonic acidemia are high, genetic counseling and prenatal diagnosis are frequently sought by families with 1 or more affected children. The prenatal diagnosis is made on a dual, complementary approach: enzymatic assays in cultured amniocytes or molecular analysis for previously identified familial mutations and direct chemical determination of MMA in cell-free supernatant of amniotic fluid from amniocentesis between 16 and 19 weeks of gestational age.
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.
<1.50 nmol/mL
Interpretation Provides information to assist in interpretation of the test results
A significantly increased amniotic fluid methylmalonic acid concentration supports a diagnosis of methylmalonic acidemia
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
If termination is under consideration, validation of an abnormal result should be done by molecular analysis for previously identified familial mutations or assay of (14)C-propionate fixation and cobalamin uptake in cultured amniocytes, and no medical action should be undertaken before the completion of all in vitro studies.
A prenatal diagnosis of methylmalonic acidemia is made only if there is a commitment to perform molecular analysis for previously identified familial mutations or have the amniocytes analyzed at an independent laboratory (not currently offered at Mayo Medical Laboratories with the exception of MAHMS/89436 Methylmalonic Aciduria and Homocystinuria, cblC Type, Full Gene Analysis).
Previous knowledge of the complementation group (typically labeled as mut0, mut-, CblA, CblB, CblC, etc), associated homocystinuria, responsiveness to vitamin B12 of the affected child, and B12 intake of the mother during the pregnancy are critical to secure an accurate prenatal diagnosis.
Supportive Data
We have performed more than 60 prenatal diagnoses of methylmalonic acidemia, and identified 13 affected fetuses. Currently, a finding of elevated methylmalonic acid is verified by measuring the concentrations of propionylcarnitine and, if applicable, homocysteine using mass spectrometry-tandem mass spectrometry methods.
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 Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID) Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Companies, 2008, Chapter 94 pp 1-47
2. Sweetman L, Rinaldo P: Prenatal diagnosis of organic acidemias with amniotic fluid. Organic Acidemia Association Newsletter 2000;10:8-9
3. Lacey J, Magera M, Matern D: 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
4. Evans MI, Duquette DA, Rinaldo P, et al: Modulation of B12 dosage and response in fetal treatment of methylmalonic aciduria (MMA): titration of treatment dose to serum and urine MMA. Fetal Diagn Ther 1997;12:21-23
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 micro) 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 to 73 m/z and 120 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 M, Matern J: 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)
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
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.
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.
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.
83921
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 |
|---|---|---|
| 81921 | Methylmalonic Acid, AF | 34627-0 |
| 21121 | Interpretation | 59462-2 |
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