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Test ID: MMAS Methylmalonic Acid, Quantitative, Serum

Reporting Name

Methylmalonic Acid, QN, S

Useful For

Evaluating children with signs and symptoms of methylmalonic acidemia using serum specimens

 

Evaluating individuals with signs and symptoms associated with a variety of causes of vitamin B12 (cobalamin) deficiency

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 deficiencies of vitamin B12 are much more common and can be due to intestinal malabsorption, impaired digestion, or poor diet. Older adult 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 kidney 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 vitamin B12 deficiency than direct vitamin B12 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 vitamin B12 (cobalamin) deficiency.

Report Available

3 to 5 days

Day(s) Performed

Monday through Friday

Clinical Reference

1. Fenton WA, Gravel RA, Rosenblatt DS: Disorders of propionate and methylmalonate metabolism. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill, 2019. Accessed October 6, 2021. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225086103&bookid=2709

2. Klee GG: Cobalamin and folate evaluation measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem. 2000 Aug;46(8):1277-1283

3. Watkins D, Rosenblatt DS: Inherited disorders of folate and cobalamin transport and metabolism. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill, 2019. Accessed October 6, 2021. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225548307&bookid=2709

4. Vashi P, Edwin P, Popiel B, et al. Methylmalonic acid and homocysteine as indicators of vitamin B-12 deficiency in cancer. PLoS One. 2016 Jan 25;11(1):e0147843

Method Name

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

Specimen Type

Serum


Specimen Required


Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

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

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 US 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

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)

-Biochemical Genetics Test Request (T798)

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Movement-Disorders, mml-Demyelinating-Diseases, mml-Neuroimmunology, mml-Neuromuscular, mml-Autonomic, mml-Pediatric, mml-Neurometabolic, mml-Neuro-ophthalmology