Test ID: MMAS Methylmalonic Acid, Quantitative, Serum
Reporting Name
Methylmalonic Acid, QN, SUseful For
Evaluating children with signs and symptoms of methylmalonic acidemia
Evaluating individuals with signs and symptoms associated with a variety of causes of cobalamin (vitamin B12) deficiency
Specimen Type
SerumSpecimen Required
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1.5 mL
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 48 days | |
Ambient | 48 days | ||
Frozen | 48 days |
Reference Values
≤0.40 nmol/mL
Day(s) and Time(s) Performed
Monday, Thursday; Continuously until 12 p.m.
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
83921
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
MMAS | Methylmalonic Acid, QN, S | 13964-2 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
80289 | Methylmalonic Acid, QN, S | 13964-2 |
Clinical Information
Elevated levels of methylmalonic acid (MMA) result from inherited defects of enzymes involved in MMA metabolism or inherited or acquired deficiencies of vitamin B12 (cobalamin) or its downstream metabolites. Acquired nutritional deficiencies are much more common than inherited defects 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, 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.
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.
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.
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 https://ommbid.mhmedical.com/book.aspx?bookid=2709#225069419
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. Watkins D, Rosenblatt DS: Inherited Disorders of Folate and Cobalamin Transport and Metabolism. In Scriver's 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 https://ommbid.mhmedical.com/book.aspx?bookid=2709#225069419
Analytic Time
3 days (not reported on Saturday or Sunday)Method Name
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Forms
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-General Request (T239)
-Benign Hematology Test Request (T755)
mml-benign-hematology-disorders