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Test ID: MMAAF Methylmalonic Acid (MMA), Amniotic Fluid

Reporting Name

Methylmalonic Acid, AF

Useful For

Specific prenatal diagnostic marker for methylmalonic acidemia

Specimen Type

Amniotic Fld

Advisory Information

Mayo genetic counselor or consultant approval is required prior to ordering test, call 800-533-1710.

Specimen Required

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.

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time
Amniotic Fld Frozen (preferred) 45 days
  Refrigerated  45 days
  Ambient  72 hours

Reference Values

<1.50 nmol/mL

Day(s) and Time(s) Performed

Monday through Friday; Continuously

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.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
MMAAF Methylmalonic Acid, AF In Process


Result ID Test Result Name Result LOINC Value
81921 Methylmalonic Acid, AF 34627-0
21121 Interpretation 59462-2

Clinical Information

Methylmalonic acid (MMA) is a specific diagnostic marker for the group of disorders collectively called methylmalonic acidemia, which includes 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 in 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, thousands 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 lifelong 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.


A significantly increased amniotic fluid methylmalonic acid concentration supports a diagnosis of methylmalonic acidemia.

Clinical Reference

1. Fenton WA, Gravel RA, Rosenblatt DS: Disorders of Propionate and Methylmalonate Metabolism. In The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, NY, McGraw-Hill, 2014. Accessed 08/17/2017. Available at

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

Analytic Time

2 days

Method Name

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


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 (T576) is available in Special Instructions.

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: